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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main NSCLC page for current regimens.

26 regimens on this page 43 variants on this page

Neoadjuvant therapy

MIC

MIC: Mitomycin, Ifosfamide, Cisplatin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Rosell et al. 1994	1989-1991	Phase 3 (E-esc)	No preoperative therapy	Superior OS
Depierre et al. 2002	1991-1997	Phase 3 (E-esc)	No preoperative therapy	Did not meet primary endpoint of OS

Chemotherapy

Mitomycin (Mutamycin) 6 mg/m² IV once on day 1
Ifosfamide (Ifex) 3000 mg/m² IV over 3 hours once on day 1
Cisplatin (Platinol) 50 mg/m² IV over 60 minutes once on day 1

Supportive therapy

Mesna (Mesnex) 1000 mg/m² IV over 3 hours once on day 1, admixed with ifosfamide
Metoclopramide (Reglan) 3 mg/kg IV, given 30 minutes prior and 90 minutes after chemotherapy
Dexamethasone (Decadron) 20 mg IV once, given 30 minutes prior to chemotherapy

21-day cycle for 3 cycles

Subsequent treatment

Surgery

References

Rosell R, Gómez-Codina J, Camps C, Maestre J, Padille J, Cantó A, Mate JL, Li S, Roig J, Olazábal A, Canela M, Ariza A, Skacel Z, Morera-Prat J, Abad A. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med. 1994 Jan 20;330(3):153-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Depierre A, Milleron B, Moro-Sibilot D, Chevret S, Quoix E, Lebeau B, Braun D, Breton JL, Lemarié E, Gouva S, Paillot N, Bréchot JM, Janicot H, Lebas FX, Terrioux P, Clavier J, Foucher P, Monchâtre M, Coëtmeur D, Level MC, Leclerc P, Blanchon F, Rodier JM, Thiberville L, Villeneuve A, Westeel V, Chastang C; IFCT. Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. J Clin Oncol. 2002 Jan 1;20(1):247-53. link to original article PubMed

Adjuvant therapy

Radiation therapy

RT: Radiation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Keller et al. 2000 (ECOG E3590)	1991-1997	Phase 3 (C)	EP & RT	Did not meet endpoint of OS

Preceding treatment

Complete surgical resection

Radiotherapy

Radiation therapy, 180 cGy fractions x 28 fractions (total dose: 5040 cGy)

5-week course

References

ECOG E3590: Keller SM, Adak S, Wagner H, Herskovic A, Komaki R, Brooks BJ, Perry MC, Livingston RB, Johnson DH; ECOG. A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer. N Engl J Med. 2000 Oct 26;343(17):1217-22. link to original article dosing details in abstract have been reviewed by our editors PubMed

Induction therapy for locally advanced disease

MIC

MIC: Mitomycin, Ifosfamide, Cisplatin
MIP: Mitomycin, Ifosfamide, Platinol (Cisplatin)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sculier et al. 1999	1989-1996	Non-randomized part of phase 3 RCT
Sculier et al. 2004	1996-2002	Phase 3 (C)	SuperMIP	Did not meet primary endpoint of OS

Chemotherapy

Mitomycin (Mutamycin) 6 mg/m² IV bolus once on day 1, given first
Ifosfamide (Ifex) 3000 mg/m² IV over 3 hours once on day 1, given second
Cisplatin (Platinol) 50 mg/m² IV over 60 minutes once on day 1, given third, 3 hours after the end of ifosfamide infusion

Supportive therapy

Mesna (Mesnex) 1000 mg/m² IV over 3 hours once on day 1, given with ifosfamide, then 500 mg/m² IV bolus at four and eight hours after ifosfamide
Lorazepam (Ativan)
Metoclopramide (Reglan)
Dexamethasone (Decadron)

21- to 28-day cycle for 3 cycles

Subsequent treatment

Sculier et al. 1999: MIP continuation x 3 versus RT consolidation
Sculier et al. 2004: RT consolidation

References

Sculier JP, Paesmans M, Lafitte JJ, Baumöhl J, Thiriaux J, van Cutsem O, Recloux P, Bureau G, Berchier MC, Zacharias C, Mommen P, Bosschaerts T, Berghmans T, van Houtte P, Ninane V, Klastersky J; European Lung Cancer Working Party. A randomised phase III trial comparing consolidation treatment with further chemotherapy to chest irradiation in patients with initially unresectable locoregional non-small-cell lung cancer responding to induction chemotherapy. Ann Oncol. 1999 Mar;10(3):295-303. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Sculier JP, Lafitte JJ, Berghmans T, Van Houtte P, Lecomte J, Thiriaux J, Efremidis A, Koumakis G, Giner V, Richez M, Corhay JL, Wackenier P, Lothaire P, Paesmans M, Mommen P, Ninane V; European Lung Cancer Working Party. A phase III randomised study comparing two different dose-intensity regimens as induction chemotherapy followed by thoracic irradiation in patients with advanced locoregional non-small-cell lung cancer. Ann Oncol. 2004 Mar;15(3):399-409. link to original article dosing details in manuscript have been reviewed by our editors PubMed

PEV

PEV: Platinol (Cisplatin), Etoposide, Vinblastine

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kim et al. 2002	1988-1992	Phase 3 (E-esc)	No induction chemotherapy	Might have superior OS

Chemotherapy

Cisplatin (Platinol) 20 mg/m² IV once per day on days 1 to 5
Etoposide (Vepesid) 100 mg/m² IV once per day on days 2 to 4
Vinblastine (Velban) 6 mg/m² IV once on day 1

21-day cycle for 3 cycles

Subsequent treatment

RT consolidation

References

Kim TY, Yang SH, Lee SH, Park YS, Im YH, Kang WK, Ha SH, Park CI, Heo DS, Bang YJ, Kim NK. A phase III randomized trial of combined chemoradiotherapy versus radiotherapy alone in locally advanced non-small-cell lung cancer. Am J Clin Oncol. 2002 Jun;25(3):238-43. link to original article PubMed

Definitive therapy for locally advanced disease

MVP & RT

MVP & RT: Mitomycin, Vindesine, Platinol (Cisplatin), Radiation Therapy

Regimen variant #1

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Furuse et al. 1999 (JCOG9202)	1992-1994	Phase 3 (E-switch-ic)	MVP, then RT	Seems to have superior OS

Chemotherapy

Mitomycin (Mutamycin) 8 mg/m² IV once per day on days 1 & 29
Vindesine (Eldisine) 3 mg/m² IV once per day on days 1, 8, 29, 36
Cisplatin (Platinol) 80 mg/m² IV once per day on days 1 & 29

Radiotherapy

Concurrent External beam radiotherapy 5600 cGy in 28 fractions, given on days 1 to 5, 8 to 12, 15 to 19, 29 to 33, 36 to 40, 43 to 46

46-day course

Regimen variant #2

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Yamamoto et al. 2010 (WJTOG0105)	2001-2005	Phase 3 (C)	1. CP & RT 2. Carboplatin, Irinotecan, RT	Inconclusive whether non-inferior OS (primary endpoint)

Chemotherapy

Mitomycin (Mutamycin) 8 mg/m² IV once on day 1
Vindesine (Eldisine) 3 mg/m² IV once per day on days 1 & 8
Cisplatin (Platinol) 80 mg/m² IV once on day 1

Radiotherapy

Concurrent External beam radiotherapy as follows (total dose 6000 cGy):
- Cycles 1 & 3: 200 cGy per fraction x 15 fractions, given on days 2 to 6, 9 to 13, 16 to 20

28-day cycle for 4 cycles

References

JCOG9202: Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, Katagami N, Ariyoshi Y. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999 Sep;17(9):2692-9. link to original article dosing details in abstract have been reviewed by our editors PubMed
WJTOG0105: Yamamoto N, Nakagawa K, Nishimura Y, Tsujino K, Satouchi M, Kudo S, Hida T, Kawahara M, Takeda K, Katakami N, Sawa T, Yokota S, Seto T, Imamura F, Saka H, Iwamoto Y, Semba H, Chiba Y, Uejima H, Fukuoka M. Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer: West Japan Thoracic Oncology Group WJTOG0105. J Clin Oncol. 2010 Aug 10;28(23):3739-45. Epub 2010 Jul 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00144053
1. Update: Zenke Y, Tsuboi M, Chiba Y, Tsujino K, Satouchi M, Sawa K, Shimizu J, Daga H, Fujimoto D, Mori M, Aoki T, Sawa T, Omori S, Saka H, Iwamoto Y, Okuno M, Hirashima T, Kashiwabara K, Tachihara M, Yamamoto N, Nakagawa K. Effect of Second-generation vs Third-generation Chemotherapy Regimens With Thoracic Radiotherapy on Unresectable Stage III Non-Small-Cell Lung Cancer: 10-Year Follow-up of a WJTOG0105 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Jun 1;7(6):904-909. link to original article link to PMC article PubMed

Maintenance after definitive therapy for inoperable disease

BCG vaccine monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pines 1976	1970-1973	Randomized (E-esc)	Observation	Seems to have superior OS

Preceding treatment

RT consolidation

Immunotherapy

BCG vaccine

References

Pines A. A 5-year controlled study of BCG and radiotherapy inoperable lung cancer. Lancet. 1976 Feb 21;1(7956):380-1. link to original article PubMed

Advanced or metastatic disease, first-line

CAMP

CAMP: Cyclophosphamide, Adriamycin (Doxorubicin), Methotrexate, Procarbazine

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Bitran et al. 1978	1975-1977	Non-randomized
Ruckdeschel et al. 1986 (ECOG E1581)	1981-1983	Randomized (E-esc)	1. MVP 2. EC 3. VC	Did not meet primary endpoint

Chemotherapy

Cyclophosphamide (Cytoxan) 300 mg/m² IV push once per day on days 1 & 8
Doxorubicin (Adriamycin) 20 mg/m² IV push once per day on days 1 & 8 (maximum cumulative dose of 450 mg/m²)
Methotrexate (MTX) 15 mg/m² IV push once per day on days 1 & 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 10 or days 2 to 11

28-day cycles

References

Bitran JD, Desser RK, DeMeester T, Golomb HM. Metastatic non-oat-cell bronchogenic carcinoma: therapy with cyclophosphamide, doxorubicin, methotrexate, and procarbazine (CAMP). JAMA. 1978 Dec 15;240(25):2743-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
ECOG E1581: Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Carboplatin & Cisplatin

CC: Cisplatin & Carboplatin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sculier et al. 1998	1990-1995	Phase 3 (C)	CCI	Inferior ORR

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Carboplatin (Paraplatin) 200 mg/m² IV over 30 minutes once on day 1
Cisplatin (Platinol) 30 mg/m² IV over 15 minutes once per day on days 2 & 3

21- to 28-day cycles

References

Sculier JP, Paesmans M, Thiriaux J, Lecomte J, Bureau G, Giner V, Efremidis A, Lafitte JJ, Berchier MC, Alexopoulos CG, Zacharias C, Mommen P, Ninane V, Klastersky J; European Lung Cancer Working Party. Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. J Clin Oncol. 1998 Apr;16(4):1388-96. link to original article dosing details in manuscript have been reviewed by our editors PubMed

CCI

CCI: Cisplatin, Carboplatin, Ifosfamide

Regimen variant #1

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sculier et al. 2002	1998-2000	Phase 3 (C)	1. CCG 2. IG	Did not meet primary endpoint of OS

Chemotherapy

Carboplatin (Paraplatin) AUC 3 IV over 30 minutes once on day 1, given second
Cisplatin (Platinol) 60 mg/m² IV over 60 minutes once on day 1, given third
Ifosfamide (Ifex) 4500 mg/m² IV over 3 hours once on day 1, given first

Supportive therapy

Mesna (Mesnex)

28-day cycles

Regimen variant #2

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sculier et al. 1998	1990-1995	Phase 3 (E-esc)	CC	Superior ORR

Chemotherapy

Carboplatin (Paraplatin) 200 mg/m² IV over 30 minutes once on day 1, given first
Cisplatin (Platinol) 30 mg/m² IV over 15 minutes once per day on days 2 & 3, given first
Ifosfamide (Ifex) 1500 mg/m² IV over 3 hours once per day on days 1 to 3, given second

Supportive therapy

Mesna (Mesnex) 300 mg/m² IV once prior to first dose of ifosfamide, then 300 mg/m² IV every 4 hours for 72 hours

21- to 28-day cycles

References

Sculier JP, Paesmans M, Thiriaux J, Lecomte J, Bureau G, Giner V, Efremidis A, Lafitte JJ, Berchier MC, Alexopoulos CG, Zacharias C, Mommen P, Ninane V, Klastersky J; European Lung Cancer Working Party. Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. J Clin Oncol. 1998 Apr;16(4):1388-96. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Sculier JP, Lafitte JJ, Lecomte J, Berghmans T, Thiriaux J, Florin MC, Efremidis A, Alexopoulos CG, Recloux P, Ninane V, Mommen P, Paesmans M, Klastersky J; European Lung Cancer Working Party. A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer. Ann Oncol. 2002 Jun;13(6):874-82. link to original article dosing details in manuscript have been reviewed by our editors PubMed

CISCA

CISCA: CISplatin, Cyclophosphamide, Adriamycin (Doxorubicin)
CAP: Cyclophosphamide, Adriamycin (Doxorubicin), Platinol (Cisplatin)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Robert et al. 1984	1978-1981	Phase 3 (C)	1. Cyclophosphamide & Doxorubicin (AC) 2. CAMF	Did not meet endpoint of OS
Miller et al. 1986 (SWOG S8012)	1980-1983	Phase 3 (C)	1. FOMi 2. FOMi/CAP	Seems to have inferior OS

Chemotherapy

Cyclophosphamide (Cytoxan) 400 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 40 mg/m² IV once on day 1
Cisplatin (Platinol) 40 mg/m² IV once on day 1

21-day cycles

References

Robert F, Omura GA, Birch R, Krauss S, Oldham R; SECG. Randomized phase III comparison of three doxorubicin-based chemotherapy regimens in advanced non-small cell lung cancer: a Southeastern Cancer Study Group trial. J Clin Oncol. 1984 May;2(5):391-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed
SWOG S8012: Miller TP, Chen TT, Coltman CA Jr, O'Bryan RM, Vance RB, Weiss GB, Fletcher WS, Stephens RL, Livingston RB. Effect of alternating combination chemotherapy on survival of ambulatory patients with metastatic large-cell and adenocarcinoma of the lung: a Southwest Oncology Group Study. J Clin Oncol. 1986 Apr;4(4):502-8. link to original article PubMed

Cisplatin monotherapy

Regimen variant #1, 75 q3wk x 8

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
von Pawel et al. 2000 (CATAPULT I)	Not reported	Phase 3 (C)	Cisplatin & Tirapazamine	Inferior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once on day 1

21-day cycle for up to 8 cycles

Regimen variant #2, 100 q3wk

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Gatzemeier et al. 2000	1995-01 to 1996-04	Phase 3 (C)	Cisplatin & Paclitaxel	Seems to have inferior TTP

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 30 minutes once on day 1

21-day cycle for up to 6 cycles

Regimen variant #3, 100 q4wk

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Gandara et al. 1993	1988-1990	Phase 3 (C)	1. HDCP 2. HDCP-M	Did not meet endpoint of OS
Wozniak et al. 1998 (SWOG S9308)	1993-1995	Phase 3 (C)	CVb	Inferior OS
Sandler et al. 2000	1995-1997	Phase 3 (C)	GC	Inferior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 30 to 120 minutes once on day 1

28-day cycle for 6 cycles (Sandler et al. 2000) or indefinitely

References

Gandara DR, Crowley J, Livingston RB, Perez EA, Taylor CW, Weiss G, Neefe JR, Hutchins LF, Roach RW, Grunberg SM, Braun TJ, Natale RB, Balcerzak SP; SWOG. Evaluation of cisplatin intensity in metastatic non-small-cell lung cancer: a phase III study of the Southwest Oncology Group. J Clin Oncol. 1993 May;11(5):873-8. link to original article PubMed
SWOG S9308: Wozniak AJ, Crowley JJ, Balcerzak SP, Weiss GR, Spiridonidis CH, Baker LH, Albain KS, Kelly K, Taylor SA, Gandara DR, Livingston RB; SWOG. Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. J Clin Oncol. 1998 Jul;16(7):2459-65. link to original article dosing details in abstract have been reviewed by our editors PubMed
Sandler AB, Nemunaitis J, Denham C, von Pawel J, Cormier Y, Gatzemeier U, Mattson K, Manegold C, Palmer MC, Gregor A, Nguyen B, Niyikiza C, Einhorn LH. Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2000 Jan;18(1):122-30. link to original article dosing details in manuscript have been reviewed by our editors PubMed
CATAPULT I: von Pawel J, von Roemeling R, Gatzemeier U, Boyer M, Elisson LO, Clark P, Talbot D, Rey A, Butler TW, Hirsh V, Olver I, Bergman B, Ayoub J, Richardson G, Dunlop D, Arcenas A, Vescio R, Viallet J, Treat J. Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group: cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors. J Clin Oncol. 2000 Mar;18(6):1351-9. link to original article dosing details in abstract have been reviewed by our editors PubMed
Gatzemeier U, von Pawel J, Gottfried M, ten Velde GP, Mattson K, de Marinis F, Harper P, Salvati F, Robinet G, Lucenti A, Bogaerts J, Gallant G. Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Oct 1;18(19):3390-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Cisplatin & Pemetrexed

Pem-Cis: Pemetrexed & Cisplatin
Cis-Pem: Cisplatin & Pemetrexed

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Scagliotti et al. 2008 (JMDB)	2004-07 to 2005-12	Phase 3 (E-RT-switch-ic)	Cisplatin & Gemcitabine	Seems to have non-inferior OS (primary endpoint) Median OS: 10.3 vs 10.3 mo (HR 0.94, 95% CI 0.84-1.05)

Note: although this regimen is still current for nonsquamous NSCLC, the JMDB trial was unselected by histology.

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once on day 1
Pemetrexed (Alimta) 500 mg/m² IV once on day 1

Supportive therapy

Cyanocobalamin (Vitamin B12) 1000 mcg IM every 9 weeks, first dose 1 to 2 weeks prior to pemetrexed
Folic acid 350 mcg to 1 mg PO once per day
Dexamethasone (Decadron) 4 mg PO twice to day on days -1 to 2

21-day cycle for 6 cycles

References

JMDB: Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. Epub 2008 May 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Cisplatin & Vinblastine

VP: Vinblastine & Platinol (Cisplatin)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kosty et al. 1994 (CALGB 8931)	1989-1991	Phase 3 (C)	VP & Hydrazine	Did not meet primary endpoint of OS

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1
Vinblastine (Velban) as follows:
- Cycle 1: 5 mg/m² IV once per day on days 1, 8, 15, 22
- Cycle 2 onwards: 5 mg/m² IV once per day on days 1 & 15

28-day cycles

References

CALGB 8931: Kosty MP, Fleishman SB, Herndon JE 2nd, Coughlin K, Kornblith AB, Scalzo A, Morris JC, Mortimer J, Green MR; CALGB. Cisplatin, vinblastine, and hydrazine sulfate in advanced, non-small-cell lung cancer: a randomized placebo-controlled, double-blind phase III study of the Cancer and Leukemia Group B. J Clin Oncol. 1994 Jun;12(6):1113-20. link to original article dosing details in abstract have been reviewed by our editors PubMed

Cisplatin & Vindesine

VP: Vindesine & Platinol (Cisplatin)
VdsC: Vindesine & Cisplatin

Regimen variant #1, 80/3

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Masutani et al. 1999	1987-1992	Phase 3 (C)	1. PVI 2. PVM	Did not meet endpoint of OS
Negoro et al. 2003	1995-1998	Phase 3 (C)	1. Cisplatin & Irinotecan	Did not meet primary endpoint of OS
Negoro et al. 2003	1995-1998	Phase 3 (C)	2. Irinotecan	Not reported
Kubota et al. 2004	1998-2000	Phase 3 (E-switch-ic)	Cisplatin & Docetaxel	Seems to have inferior OS (primary endpoint)

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV over 1 to 2 hours once on day 1
Vindesine (Eldisine) 3 mg/m² IV bolus once per day on days 1, 8, 15

28-day cycle for 2 or more cycles

Regimen variant #2, 100/3; split-dose cisplatin

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kodani et al. 2002	1987-1992	Phase 3 (C)	PVI	Did not meet endpoint of ORR

Chemotherapy

Cisplatin (Platinol) 20 mg/m² IV once per day on days 1 to 5
Vindesine (Eldisine) 3 mg/m² IV once per day on days 1 & 8

28-day cycle for 5 cycles

Regimen variant #3, 100/3; capped vindesine

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Vansteenkiste et al. 2001	1996-1999	Phase 3 (C)	Gemcitabine	Seems to have inferior clinical benefit

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 1 to 4 hours once on day 1
Vindesine (Eldisine) 3 mg/m² (maximum dose of 5 mg) IV once per day on days 1 & 15

28-day cycles

Regimen variant #4, 120/3, 4-week induction

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Rapp et al. 1988	1983-1986	Phase 3 (E-esc)	Best supportive care	Superior OS

Chemotherapy

Cisplatin (Platinol) as follows:
- Cycle 1: 120 mg/m² IV once per day on days 1 & 29
- Cycle 2 onwards: 120 mg/m² IV once on day 1
Vindesine (Eldisine) as follows:
- Cycle 1: 3 mg/m² IV once per day on days 1, 8, 15, 22, 36, 50
- Cycle 2 onwards: 3 mg/m² IV once per day on days 1, 15, 29

9-week course, then 42-day cycles

Regimen variant #5, 120/3, 5-week induction

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Ruckdeschel et al. 1986 (ECOG E1581)	1981-1983	Phase 3 (E-de-esc)	1. CAMP 2. EC 3. MVP	Did not meet primary endpoint

Chemotherapy

Cisplatin (Platinol) as follows:
- Cycle 1: 120 mg/m² IV once per day on days 1 & 29
- Cycle 2 onwards: 120 mg/m² IV once on day 1
Vindesine (Eldisine) as follows:
- Cycle 1: 3 mg/m² IV once per day on days 1, 8, 15, 22, 29, 43, 57
- Cycle 2 onwards: 3 mg/m² IV once per day on days 8, 22, 36

10-week course, then 42-day cycles

Regimen variant #6, 120/3, 6-week induction

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Le Chevalier et al. 1994	1989-1991	Phase 3 (C)	1. CVb	Seems to have inferior OS
Le Chevalier et al. 1994	1989-1991	Phase 3 (C)	2. Vinorelbine	Not reported

Chemotherapy

Cisplatin (Platinol) as follows:
- Cycle 1: 120 mg/m² IV once per day on days 1 & 29
- Cycle 2 onwards: 120 mg/m² IV once on day 29
Vindesine (Eldisine) as follows:
- Cycle 1: 3 mg/m² IV once per day on days 1, 8, 15, 22, 29, 36
- Cycle 2 onwards: 3 mg/m² IV once per day on days 1, 15, 29

42-day cycles

References

ECOG E1581: Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Rapp E, Pater JL, Willan A, Cormier Y, Murray N, Evans WK, Hodson DI, Clark DA, Feld R, Arnold AM, Ayoub JI, Wilson KS, Latreille J, Wierzbicki RF, Hill DP. Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial. J Clin Oncol. 1988 Apr;6(4):633-41. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Le Chevalier T, Brisgand D, Douillard JY, Pujol JL, Alberola V, Monnier A, Riviere A, Lianes P, Chomy P, Cigolari S, Gottfried M, Ruffle P, Panizo A, Gaspard MH, Ravaioli A, Besenval M, Besson F, Martinez A, Berthaud P, Tursz T. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients. J Clin Oncol. 1994 Feb;12(2):360-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Masutani M, Akusawa H, Kadota A, Ohchi Y, Takahashi N, Tanigawa S, Koya Y, Horie T. A phase III randomized trial of cisplatin plus vindesine versus cisplatin plus vindesine plus mitomycin C versus cisplatin plus vindesine plus ifosfamide for advanced non-small-cell lung cancer. Respirology. 1996 Mar;1(1):49-54. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Vansteenkiste JF, Vandebroek JE, Nackaerts KL, Weynants P, Valcke YJ, Verresen DA, Devogelaere RC, Marien SA, Humblet YP, Dams NL; Leuven Lung Cancer Group. Clinical-benefit response in advanced non-small-cell lung cancer: a multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine. Ann Oncol. 2001 Sep;12(9):1221-30. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Kodani T, Ueoka H, Kiura K, Tabata M, Takigawa N, Segawa Y, Moritaka T, Hiraki S, Harada M, Tanimoto M. A phase III randomized trial comparing vindesine and cisplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer: long-term follow-up results and analysis of prognostic factors. Lung Cancer. 2002 Jun;36(3):313-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Negoro S, Masuda N, Takada Y, Sugiura T, Kudoh S, Katakami N, Ariyoshi Y, Ohashi Y, Niitani H, Fukuoka M; CPT-11 Lung Cancer Study Group West. Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer. Br J Cancer. 2003 Feb 10;88(3):335-41. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, Sugiura T, Kawahara M, Yokoyama A, Yokota S, Yoneda S, Matsui K, Kudo S, Shibuya M, Isobe T, Segawa Y, Nishiwaki Y, Ohashi Y, Niitani H; Japanese Taxotere Lung Cancer Study Group. Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: the Japanese Taxotere Lung Cancer Study Group. J Clin Oncol. 2004 Jan 15;22(2):254-61. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Docetaxel monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Roszkowski et al. 2000	1995 to not reported	Phase 3 (E-esc)	Best supportive care	Seems to have superior OS
Georgoulias et al. 2007	2002-2004	Phase 3 (C)	DG	Seems to have inferior OS

Chemotherapy

Docetaxel (Taxotere) 100 mg/m² IV over 60 minutes once on day 1

21-day cycles

References

Roszkowski K, Pluzanska A, Krzakowski M, Smith AP, Saigi E, Aasebo U, Parisi A, Pham Tran N, Olivares R, Berille J. A multicenter, randomized, phase III study of docetaxel plus best supportive care versus best supportive care in chemotherapy-naive patients with metastatic or non-resectable localized non-small cell lung cancer (NSCLC). Lung Cancer. 2000 Mar;27(3):145-57. link to original article dosing details in abstract have been reviewed by our editors PubMed
Georgoulias V, Androulakis N, Kotsakis A, Hatzidaki D, Syrigos K, Polyzos A, Agelidou A, Varthalitis I, Ziras N, Agelidou M, Chandrinos V, Boukovinas I, Geroyianni A, Vamvakas L, Mavroudis D. Docetaxel versus docetaxel plus gemcitabine as front-line treatment of patients with advanced non-small cell lung cancer: a randomized, multicenter phase III trial. Lung Cancer. 2008 Jan;59(1):57-63. Epub 2007 Aug 31. link to original article dosing details in abstract have been reviewed by our editors PubMed

Docetaxel & Gemcitabine

DG: Docetaxel & Gemcitabine

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Georgoulias et al. 2007	2002-2004	Phase 3 (E-esc)	Docetaxel	Seems to have superior OS (primary endpoint) Median OS: 9.4 vs 8.3 mo

Note: while this was the superior arm of a phase 3 RCT, the comparator (single-agent docetaxel) is not usually used in the first-line treatment and this regimen is not currently recommended by ESMO guidelines.

Chemotherapy

Docetaxel (Taxotere) 1100 mg/m² IV once per day on days 1 & 8
Gemcitabine (Gemzar) 75 mg/m² IV once on day 8

21-day cycles

References

Georgoulias V, Androulakis N, Kotsakis A, Hatzidaki D, Syrigos K, Polyzos A, Agelidou A, Varthalitis I, Ziras N, Agelidou M, Chandrinos V, Boukovinas I, Geroyianni A, Vamvakas L, Mavroudis D. Docetaxel versus docetaxel plus gemcitabine as front-line treatment of patients with advanced non-small cell lung cancer: a randomized, multicenter phase III trial. Lung Cancer. 2008 Jan;59(1):57-63. Epub 2007 Aug 31. link to original article dosing details in abstract have been reviewed by our editors PubMed

FULV

FULV: 5-FU & LeucoVorin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Crawford et al. 1996	1990-1992	Randomized (C)	Vinorelbine	Seems to have inferior OS

Note: To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Fluorouracil (5-FU) 425 mg/m² IV once per day on days 1 to 5, given second
Leucovorin (Folinic acid) 20 mg/m² IV bolus once per day on days 1 to 5, given first

28-day cycles

References

Crawford J, O'Rourke M, Schiller JH, Spiridonidis CH, Yanovich S, Ozer H, Langleben A, Hutchins L, Koletsky A, Clamon G, Burman S, White R, Hohneker J. Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer. J Clin Oncol. 1996 Oct;14(10):2774-84. Erratum in: J Clin Oncol 1996 Dec;14(12):3175. Spiridonitis CH [corrected to Spiridonidis CH]. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Ifosfamide & Gemcitabine

IG: Ifosfamide & Gemcitabine

Regimen variant #1, 3000/1000

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Berghmans et al. 2013 (ELCWP-01041)	2003-2009	Phase 3 (C)	1. GIP 2. DP	Did not meet primary endpoint of OS

Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. Cycle length was not explicitly declared in the manuscript and was inferred from other variants.

Chemotherapy

Ifosfamide (Ifex) 3000 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV once per day on day 1, 8, 15

28-day cycles

Regimen variant #2, 4500/1000

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sculier et al. 2002	1998-2000	Phase 3 (E-esc)	1. CCI 2. CCG	Did not meet primary endpoint of OS

Note: This was an experimental arm that did not meet its primary endpoint; included here because it was likely used to establish this regimen as a standard comparator.

Chemotherapy

Ifosfamide (Ifex) 4500 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV once per day on day 1, 8, 15

28-day cycles

References

Sculier JP, Lafitte JJ, Lecomte J, Berghmans T, Thiriaux J, Florin MC, Efremidis A, Alexopoulos CG, Recloux P, Ninane V, Mommen P, Paesmans M, Klastersky J; European Lung Cancer Working Party. A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer. Ann Oncol. 2002 Jun;13(6):874-82. link to original article dosing details in manuscript have been reviewed by our editors PubMed
ELCWP-01041: Berghmans T, Lafitte JJ, Scherpereel A, Paesmans M, Lecomte J, Marco VG, Meert AP, Leclercq N, Sculier JP; European Lung Cancer Working Party. An ELCWP phase III trial comparing ifosfamide and cisplatin regimens in advanced NSCLC. Anticancer Res. 2013 Dec;33(12):5477-82. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00622349

Gemcitabine monotherapy

Regimen variant #1, 1000 mg/m², 3 out of 4 weeks

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Vansteenkiste et al. 2001	1996-1999	Phase 3 (E-de-esc)	Cisplatin & Vindesine	Seems to have superior clinical benefit

Note: this regimen is considered current in elderly patients or those with poor PS; these trials were unselected by these parameters.

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1, 8, 15

28-day cycles

Regimen variant #2, 1250 mg/m², 2 out of 3 weeks

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sederholm et al. 2005	1998-2001	Phase 3 (E-de-esc)	Carboplatin & Gemcitabine	Seems to have inferior OS

Note: this regimen is considered current in elderly patients or those with poor PS; these trials were unselected by these parameters.

Chemotherapy

Gemcitabine (Gemzar) 1250 mg/m² IV once per day on days 1 & 8

21-day cycles

References

Vansteenkiste JF, Vandebroek JE, Nackaerts KL, Weynants P, Valcke YJ, Verresen DA, Devogelaere RC, Marien SA, Humblet YP, Dams NL; Leuven Lung Cancer Group. Clinical-benefit response in advanced non-small-cell lung cancer: a multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine. Ann Oncol. 2001 Sep;12(9):1221-30. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, Gawande SR. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol. 2005 Nov 20;23(33):8380-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed

GIP

GIP: Gemcitabine, Ifosfamide, Platinol (Cisplatin)

Regimen

Study	Dates of enrollment	Evidence
Sculier et al. 2007	2000-2004	Non-randomized part of phase 3 RCT

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8
Ifosfamide (Ifex) 3000 mg/m² IV once on day 1
Cisplatin (Platinol) 50 mg/m² IV once on day 1

21-day cycle for 3 cycles

References

Sculier JP, Lafitte JJ, Lecomte J, Alexopoulos CG, Van Cutsem O, Giner V, Efremidis A, Berchier MC, Collon T, Meert AP, Scherpereel A, Ninane V, Paesmans M, Berghmans T; European Lung Cancer Working Party. A phase III randomised trial comparing sequential chemotherapy using cisplatin-based regimen and paclitaxel to cisplatin-based chemotherapy alone in advanced non-small-cell lung cancer. Ann Oncol. 2007 Jun;18(6):1037-42. Epub 2007 Apr 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed

MACC

MACC: Methotrexate, Adriamycin (Doxorubicin), Cyclophosphamide, CCNU (Lomustine)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Chahinian et al. 1977	Not reported	Non-randomized
Cormier et al. 1982	Not reported	Phase 3 (E-esc)	Placebo	Superior OS

Chemotherapy

Methotrexate (MTX) 40 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 40 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 400 mg/m² IV once on day 1
Lomustine (CCNU) 30 mg/m² PO once on day 1, taken on an empty stomach

21-day cycles

References

Chahinian PA, Arnold DJ, Cohen JM, Purpora DP, Jaffrey IS, Teirstein AS, Kirschner PA, Holland JF. Chemotherapy for bronchogenic carcinoma: methotrexate, doxorubicin, cyclophosphamide, and lomustine. JAMA. 1977 May 30;237(22):2392-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Cormier Y, Bergeron D, La Forge J, Lavandier M, Fournier M, Chenard J, Desmeules M. Benefits of polychemotherapy in advanced non-small-cell bronchogenic carcinoma. Cancer. 1982 Sep 1;50(5):845-9. link to original article PubMed

MIC

MIC: Mitomycin, Ifosfamide, Cisplatin
MIP: Mitomycin, Ifosfamide, Platinol (Cisplatin)

Regimen variant #1

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Danson et al. 2003	1997-2001	Phase 3 (C)	GC	Did not meet primary endpoint of OS

Chemotherapy

Mitomycin (Mutamycin) 6 mg/m² IV bolus once on day 1
Ifosfamide (Ifex) 3000 mg/m² IV once on day 1
Cisplatin (Platinol) 50 mg/m² IV once on day 1

21-day cycle for 4 cycles

Regimen variant #2

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Cullen et al. 1999 (MIC2)	1988-1996	Phase 3 (E-esc)	Best supportive care	Seems to have superior OS
Sculier et al. 2000	1995-1998	Phase 3 (C)	CarboMIP	Did not meet primary endpoint of OS
Booton et al. 2006 (BTOG1)	2001-06 to 2002-11	Phase 3 (C)	DCb	Did not meet primary endpoint of OS

Chemotherapy

Mitomycin (Mutamycin) 6 mg/m² IV bolus once on day 1, given first
Ifosfamide (Ifex) 3000 mg/m² IV over 3 hours once on day 1, given second
Cisplatin (Platinol) 60 mg/m² IV over 60 minutes once on day 1, given third, 3 hours after end of ifosfamide

Supportive therapy

Mesna (Mesnex) 1000 mg/m² IV over 3 hours once on day 1, given with ifosfamide, then 500 mg/m² IV bolus at 4 hours and 8 hours after ifosfamide

21-day cycles

Regimen variant #3, higher-dose cisplatin

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Crinò et al. 1999	1995-1997	Phase 3 (C)	Cisplatin & Gemcitabine	Seems to have inferior ORR

Chemotherapy

Mitomycin (Mutamycin) 6 mg/m² IV once on day 1
Ifosfamide (Ifex) 3000 mg/m² IV once on day 1
Cisplatin (Platinol) 100 mg/m² IV once on day 2

Supportive therapy

Mesna (Mesnex) 600 mg/m² IV once on day 1, given with ifosfamide, then 600 mg/m² IV at 4 hours and 8 hours after ifosfamide

28-day cycles

References

MIC2: Cullen MH, Billingham LJ, Woodroffe CM, Chetiyawardana AD, Gower NH, Joshi R, Ferry DR, Rudd RM, Spiro SG, Cook JE, Trask C, Bessell E, Connolly CK, Tobias J, Souhami RL. Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life. J Clin Oncol. 1999 Oct;17(10):3188-94. link to original article PubMed
Crinò L, Scagliotti GV, Ricci S, De Marinis F, Rinaldi M, Gridelli C, Ceribelli A, Bianco R, Marangolo M, Di Costanzo F, Sassi M, Barni S, Ravaioli A, Adamo V, Portalone L, Cruciani G, Masotti A, Ferrara G, Gozzelino F, Tonato M. Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol. 1999 Nov;17(11):3522-30. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Sculier JP, Lafitte JJ, Paesmans M, Thiriaux J, Alexopoulos CG, Baumöhl J, Schmerber J, Koumakis G, Florin MC, Zacharias C, Berghmans T, Mommen P, Ninane V, Klastersky J. Phase III randomized trial comparing moderate-dose cisplatin to combined cisplatin and carboplatin in addition to mitomycin and ifosfamide in patients with stage IV non-small-cell lung cancer. Br J Cancer. 2000 Nov;83(9):1128-35. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
Danson S, Middleton MR, O'Byrne KJ, Clemons M, Ranson M, Hassan J, Anderson H, Burt PA, Fairve-Finn C, Stout R, Dowd I, Ashcroft L, Beresford C, Thatcher N. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003 Aug 1;98(3):542-53. link to original article dosing details in manuscript have been reviewed by our editors PubMed
BTOG1: Booton R, Lorigan P, Anderson H, Baka S, Ashcroft L, Nicolson M, O'Brien M, Dunlop D, O'Byrne K, Laurence V, Snee M, Dark G, Thatcher N. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol. 2006 Jul;17(7):1111-9. Epub 2006 Apr 7. link to original article PubMed

MVP (Vinblastine)

MVP: Mitomycin, Vinblastine, Platinol (Cisplatin)

Regimen variant #1

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Danson et al. 2003	1997-2001	Phase 3 (C)	GC	Did not meet primary endpoint of OS

Chemotherapy

Mitomycin (Mutamycin) as follows:
- Cycles 1, 2, 4: 8 mg/m² IV bolus once on day 1
Vinblastine (Velban) 6 mg/m² (maximum dose of 10 mg) IV bolus once on day 1
Cisplatin (Platinol) 50 mg/m² IV once on day 1

21-day cycle for 4 cycles

Regimen variant #2

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Ruckdeschel et al. 1986 (ECOG E1581)	1981-1983	Phase 3 (E-de-esc)	1. CAMP 2. EC 3. VC	Did not meet primary endpoint
Bonomi et al. 1989 (ECOG E1583)	1984-01 to 1985-07	Phase 3 (C)	1. VP 2. MVP/CAMP 3. Carboplatin 4. Iproplatin	Might have inferior OS
Veeder et al. 1992	Not reported	Phase 3 (C)	Mitomycin	Might have superior OS
Smith et al. 2001	1995-1998	Phase 3 (C)	MVP x 3	Did not meet co-primary endpoint of OS
Booton et al. 2006 (BTOG1)	2001-06 to 2002-11	Phase 3 (C)	DCb	Did not meet primary endpoint of OS

Chemotherapy

Mitomycin (Mutamycin) 10 mg/m² IV over 5 to 15 minutes once on day 1
Vinblastine (Velban) 6 mg/m² IV push once on day 1
Cisplatin (Platinol) 60 mg/m² IV over 2 hours once on day 1

28-day cycles

References

ECOG E1581: Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. link to original article PubMed
ECOG E1583: Bonomi PD, Finkelstein DM, Ruckdeschel JC, Blum RH, Green MD, Mason B, Hahn R, Tormey DC, Harris J, Comis R, Glick J. Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small-cell lung cancer: a study of the Eastern Cooperative Oncology Group. J Clin Oncol. 1989 Nov;7(11):1602-13. link to original article PubMed
Veeder MH, Jett JR, Su JQ, Mailliard JA, Foley JF, Dalton RJ, Etzell PS, Marschke RF Jr, Kardinal CG, Maksymiuk AW, Ebbert LP, Tazelaar HD, Witrak GA. A phase III trial of mitomycin C alone versus mitomycin C, vinblastine, and cisplatin for metastatic squamous cell lung carcinoma. Cancer. 1992 Nov 1;70(9):2281-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Smith IE, O'Brien ME, Talbot DC, Nicolson MC, Mansi JL, Hickish TF, Norton A, Ashley S. Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin. J Clin Oncol. 2001 Mar 1;19(5):1336-43. link to original article PubMed
Danson S, Middleton MR, O'Byrne KJ, Clemons M, Ranson M, Hassan J, Anderson H, Burt PA, Fairve-Finn C, Stout R, Dowd I, Ashcroft L, Beresford C, Thatcher N. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003 Aug 1;98(3):542-53. link to original article dosing details in manuscript have been reviewed by our editors PubMed
BTOG1: Booton R, Lorigan P, Anderson H, Baka S, Ashcroft L, Nicolson M, O'Brien M, Dunlop D, O'Byrne K, Laurence V, Snee M, Dark G, Thatcher N. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol. 2006 Jul;17(7):1111-9. Epub 2006 Apr 7. link to original article PubMed

MVP (Vindesine)

MVP: Mitomycin, Vindesine, Platinol (Cisplatin)
PVM: Platinol (Cisplatin), Vindesine, Mitomycin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
González Barón et al. 1994	1989-1992	Phase 3 (E-switch-ic)	MIP	Did not meet primary endpoint of ORR
Gridelli et al. 1996	1990-1994	Phase 3 (C)	MEV	Did not meet primary endpoint of ORR
Jelić et al. 2001	1990-1996	Phase 3 (C)	MVC	Inferior OS
Boni et al. 1998	1992-1996	Phase 3 (C)	MVP; CI	Did not meet endpoint of OS

Chemotherapy

Mitomycin (Mutamycin) as follows:
- Cycles 1, 2, 4, 6: 8 mg/m² IV bolus once on day 1
Vindesine (Eldisine) as follows:
- Cycle 1: 3 mg/m² IV bolus once per day on days 1, 8, 15, 22
- Cycles 2 to 6: 3 mg/m² IV bolus once per day on days 1 & 15
Cisplatin (Platinol) 125 mg/m² IV once on day 1

28-day cycle for up to 6 cycles

References

González Barón M, Feliu J, Espinosa E, García Girón C, Blanco E, Garrido P, Colmenarejo A, Ordóñez A, Moyano A, de la Gándara I, Zamora P; ONCOPAZ Cooperative Group. Comparison of two chemotherapeutic regimens--mitomycin + vindesine + cisplatin (MVP) vs mitomycin + ifosfamide + cisplatin (MIP)--in advanced non-small-cell lung cancer. Ann Oncol. 1994 Apr;5(4):323-7. link to original article PubMed
Gridelli C, Perrone F, Palmeri S, D'Aprile M, Cognetti F, Rossi A, Gebbia V, Pepe R, Veltri E, Airoma G, Russo A, Incoronato P, Scinto AF, Palazzolo G, Natali M, Leonardi V, Gallo C, De Placido S, Bianco AR; GOSCI. Mitomycin C plus vindesine plus etoposide (MEV) versus mitomycin C plus vindesine plus cisplatin (MVP) in stage IV non-small-cell lung cancer: A phase III multicentre randomised trial. Ann Oncol. 1996 Oct;7(8):821-6. link to original article PubMed
Boni C, Savoldi L, Bisagni G, Ceci G, Crinò L, De Lisi V, Di Costanzo F, Lasagni L, Manenti AL, Moretti G, Rondini E, Sassi M, Zadro A; GOIRC. Bolus versus 5-day continuous infusion of cisplatin with mitomycin and vindesine in the treatment of advanced non-small cell lung cancer (NSCLC): a phase III prospective randomised trial of the Italian Oncology Group for Clinical Research (GOIRC). Eur J Cancer. 1998 Nov;34(12):1974-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Jelić S, Mitrović L, Radosavljević D, Elezar E, Babović N, Kovcin V, Tomasević Z, Kovacević S, Gavrilović D, Radulović S. Survival advantage for carboplatin substituting cisplatin in combination with vindesine and mitomycin C for stage IIIB and IV squamous-cell bronchogenic carcinoma: a randomized phase III study. Lung Cancer. 2001 Oct;34(1):1-13. link to original article PubMed

Paclitaxel monotherapy

Regimen variant #1, 100 mg/m², 3 out of 4 weeks

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Comella et al. 2004 (SICOG 9909)	1999-2003	Phase 3 (E-de-esc)	1. Gemcitabine	Not reported
Comella et al. 2004 (SICOG 9909)	1999-2003	Phase 3 (E-de-esc)	2. GT 3. GV	Seems to have inferior OS (primary endpoint)

Chemotherapy

Paclitaxel (Taxol) 100 mg/m² IV once per day on days 1, 8, 15

28-day cycle for up to 6 cycles

Regimen variant #2, 200 mg/m² q3wk

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Ranson et al. 2000	1995-1997	Phase 3 (E-esc)	Best supportive care	Seems to have superior OS

Chemotherapy

Paclitaxel (Taxol) 200 mg/m² IV over 3 hours once on day 1

21-day cycles

References

Ranson M, Davidson N, Nicolson M, Falk S, Carmichael J, Lopez P, Anderson H, Gustafson N, Jeynes A, Gallant G, Washington T, Thatcher N. Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 2000 Jul 5;92(13):1074-80. link to original article PubMed
SICOG 9909: Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, Cioffi R. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer. 2004 Aug 2;91(3):489-97. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed

Vindesine monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Einhorn et al. 1986	1982-1984	Phase 3 (C)	1. Cisplatin & Vindesine 2. MVP	Did not meet endpoint of OS
Furuse et al. 1996	1991-1993	Phase 3 (C)	Vinorelbine	Inferior ORR

Chemotherapy

Vindesine (Eldisine) as follows:
- Cycle 1: 3 mg/m² IV once per day on days 1, 8, 15, 22
- Cycle 2 onwards: 3 mg/m² IV once per day on days 1 & 15

28-day cycles

References

Einhorn LH, Loehrer PJ, Williams SD, Meyers S, Gabrys T, Nattan SR, Woodburn R, Drasga R, Songer J, Fisher W, Stephens D, Hui S. Random prospective study of vindesine versus vindesine plus high-dose cisplatin versus vindesine plus cisplatin plus mitomycin C in advanced non-small-cell lung cancer. J Clin Oncol. 1986 Jul;4(7):1037-43. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Furuse K, Fukuoka M, Kuba M, Yamori S, Nakai Y, Negoro S, Katagami N, Takada Y, Kinuwaki E, Kawahara M, Kubota K, Sakuma A, Niitani H; Japan Vinorelbine Lung Cancer Cooperative Study Group. Randomized study of vinorelbine (VRB) versus vindesine (VDS) in previously untreated stage IIIB or IV non-small-cell lung cancer (NSCLC). Ann Oncol. 1996 Oct;7(8):815-20. link to original article PubMed

Vinorelbine monotherapy

Regimen variant #1, 25 mg/m²/week

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Furuse et al. 1996	1991-1993	Phase 3 (E-switch-ic)	Vindesine	Superior ORR

Chemotherapy

Vinorelbine (Navelbine) 25 mg/m² IV once on day 1

7-day cycles

Regimen variant #2, 30 mg/m²/week

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Depierre et al. 1994	1989-1991	Phase 3 (C)	CVb	Inferior TTP
Le Chevalier et al. 1994	1989-1991	Phase 3 (E-de-esc)	1. Cisplatin & Vindesine	Not reported
Le Chevalier et al. 1994	1989-1991	Phase 3 (E-de-esc)	2. CVb	Inferior OS
Crawford et al. 1996	1990-1992	Randomized (E-RT-switch-ic)	FULV	Seems to have superior OS

Chemotherapy

Vinorelbine (Navelbine) 30 mg/m² IV once on day 1

7-day cycles

Regimen variant #3, 30 mg/m², 2 out of 3 weeks

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Frasci et al. 2001	Not reported	Phase 3 (C)	Gemcitabine & Vinorelbine	Inferior OS

Note: To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Vinorelbine (Navelbine) 30 mg/m² IV once per day on days 1 & 8

21-day cycles

References

Depierre A, Chastang C, Quoix E, Lebeau B, Blanchon F, Paillot N, Lemarie E, Milleron B, Moro D, Clavier J, Herman D, Tuchais E, Jacoulet P, Brechot JM, Cordier JF, Solal-Celigny P, Badri N, Besenval M. Vinorelbine versus vinorelbine plus cisplatin in advanced non-small cell lung cancer: a randomized trial. Ann Oncol. 1994 Jan;5(1):37-42. link to original article dosing details in abstract have been reviewed by our editors PubMed
Le Chevalier T, Brisgand D, Douillard JY, Pujol JL, Alberola V, Monnier A, Riviere A, Lianes P, Chomy P, Cigolari S, Gottfried M, Ruffle P, Panizo A, Gaspard MH, Ravaioli A, Besenval M, Besson F, Martinez A, Berthaud P, Tursz T. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients. J Clin Oncol. 1994 Feb;12(2):360-7. link to original article dosing details in abstract have been reviewed by our editors PubMed
Crawford J, O'Rourke M, Schiller JH, Spiridonidis CH, Yanovich S, Ozer H, Langleben A, Hutchins L, Koletsky A, Clamon G, Burman S, White R, Hohneker J. Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer. J Clin Oncol. 1996 Oct;14(10):2774-84. Erratum in: J Clin Oncol 1996 Dec;14(12):3175. Spiridonitis CH [corrected to Spiridonidis CH]. link to original article dosing details in abstract have been reviewed by our editors PubMed
Furuse K, Fukuoka M, Kuba M, Yamori S, Nakai Y, Negoro S, Katagami N, Takada Y, Kinuwaki E, Kawahara M, Kubota K, Sakuma A, Niitani H; Japan Vinorelbine Lung Cancer Cooperative Study Group. Randomized study of vinorelbine (VRB) versus vindesine (VDS) in previously untreated stage IIIB or IV non-small-cell lung cancer (NSCLC). Ann Oncol. 1996 Oct;7(8):815-20. link to original article dosing details in abstract have been reviewed by our editors PubMed
Frasci G, Lorusso V, Panza N, Comella P, Nicolella G, Bianco A, DeCataldis G, Belli M, Iannelli N, Massidda B, Mascia V, Comella G, De Lena M; Southern Italy Cooperative Oncology Group. Gemcitabine plus vinorelbine yields better survival outcome than vinorelbine alone in elderly patients with advanced non-small cell lung cancer: a Southern Italy Cooperative Oncology Group (SICOG) phase III trial. Lung Cancer. 2001 Dec;34 Suppl 4:S65-9. link to original article dosing details in abstract have been reviewed by our editors PubMed

VeIP

VeIP: Velban (Vinblastine), Ifosfamide, Platinol (Cisplatin)
VIP: Vinblastine, Ifosfamide, Platinol (Cisplatin)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kosmidis et al. 1996a	1992-1994	Phase 3 (C)	VIP-16	Did not meet primary endpoint of ORR

Chemotherapy

Vinblastine (Velban) 6 mg/m² IV once on day 1
Ifosfamide (Ifex) 3000 mg/m² IV once on day 1
Cisplatin (Platinol) 100 mg/m² IV once on day 1

21-day cycles

References

Kosmidis P, Mylonakis N, Fountzilas G, Pavlidis N, Samantas E, Karabelis A, Kattis K, Skarlos D; HeCOG. A prospective randomized phase III study in non-small-cell lung cancer comparing cisplatin, ifosfamide, vinblastine (VIP) versus cisplatin, ifosfamide and etoposide (VIP-16). Ann Oncol. 1996 Jul;7(5):517-20. link to original article dosing details in abstract have been reviewed by our editors PubMed

Maintenance after first-line therapy

Erlotinib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Cappuzzo et al. 2010 (SATURN)	2005-2008	Phase 3 (E-RT-esc)	Placebo	Superior PFS (co-primary endpoint) Median PFS: 12.3 vs 11.1 weeks (HR 0.71, 95% CI 0.62-0.82)
Pérol et al. 2012 (IFCT-GFPC 0502)	2006-2009	Phase 3 (E-esc)	1. Gemcitabine	Not reported
Pérol et al. 2012 (IFCT-GFPC 0502)	2006-2009	Phase 3 (E-esc)	2. Observation	Superior PFS (primary endpoint) Median PFS: 2.9 vs 1.9 mo (HR 0.69, 95% CI 0.54-0.88)
Cicènas et al. 2016 (IUNO)	2011-2014	Phase 3 (E-RT-switch-ic)	See link	See link

Note: while SATURN was technically a positive study for erlotinib, the median PFS gain was 1.2 weeks. This study was the basis of an FDA approval in 2010, which was later revised after the results of IUNO became available. The trials included here did not require EGFR mutation as a condition for enrollment.

Preceding treatment

SATURN and IUNO: First-line platinum-doublet therapy x 4
IFCT-GFPC 0502: First-line GC x 4

Targeted therapy

Erlotinib (Tarceva) 150 mg PO once per day on days 1 to 28

28-day cycles

References

SATURN: Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczésna A, Juhász E, Esteban E, Molinier O, Brugger W, Melezínek I, Klingelschmitt G, Klughammer B, Giaccone G; SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010 Jun;11(6):521-9. Epub 2010 May 20. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00556712
IFCT-GFPC 0502: Pérol M, Chouaid C, Pérol D, Barlési F, Gervais R, Westeel V, Crequit J, Léna H, Vergnenègre A, Zalcman G, Monnet I, Le Caer H, Fournel P, Falchero L, Poudenx M, Vaylet F, Ségura-Ferlay C, Devouassoux-Shisheboran M, Taron M, Milleron B. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2012 Oct 1;30(28):3516-24. Epub 2012 Sep 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00300586
IUNO: Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01328951

Advanced or metastatic disease, subsequent lines of therapy

Erlotinib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Shepherd et al. 2005 (NCIC-CTG BR.21)	2001-2003	Phase 3 (E-RT-esc)	Placebo	Superior OS (primary endpoint) Median OS: 6.7 vs 4.7 mo (aHR 0.70, 95% CI 0.58-0.85)
Herbst et al. 2011 (BeTa)	2005-2008	Phase 3 (C)	Erlotinib & Bevacizumab	Did not meet primary endpoint of OS
Natale et al. 2011 (ZEST)	2006-10 to 2007-11	Phase 3 (C)	Vandetanib	Did not meet primary endpoint of PFS
Ciuleanu et al. 2012 (TITAN)	2006-2010	Phase 3 (E-switch-ooc)	Investigator's choice of: 1a. Docetaxel 1b. Pemetrexed	Did not meet primary endpoint of OS
Karampeazis et al. 2013 (CT/06.05)	2006-2010	Phase 3 (E-switch-ooc)	Pemetrexed	Did not meet primary endpoint of TTP
Scagliotti et al. 2012 (SUN 1087)	2007-2009	Phase 3 (C)	Erlotinib & Sunitinib	Did not meet primary endpoint of OS
Garassino et al. 2013 (TAILOR_NSCLC)	2007-2012	Phase 3 (E-switch-ooc)	Docetaxel	Seems to have inferior OS (primary endpoint) Median OS: 5.4 vs 8.2 mo (aHR 1.37, 95% CI 1.00-1.89)
Ramalingam et al. 2012 (A7471028)	2008-2009	Randomized Phase 2 (C)	Dacomitinib	Seems to have inferior PFS
Scagliotti et al. 2015 (ADVIGO 1018)	2008-2010	Phase 3 (C)	Erlotinib & Figitumumab	Did not meet primary endpoint of OS
Kawaguchi et al. 2014 (DELTA_NSCLC)	2009-2012	Phase 3 (E-switch-ooc)	Docetaxel	Might have inferior PFS (primary endpoint)
Urata et al. 2016 (WJOG 5108L)	2009-2012	Phase 3 (C)	Gefitinib	Inconclusive whether non-inferior PFS
Smit et al. 2016 (CurrentS)	2010 to not reported	Phase 3 (C)	Erlotinib; high-dose	Did not meet primary endpoint of PFS
Wang et al. 2017a	2010-2014	Phase 3 (C)	Erlotinib, Bevacizumab, Panitumumab	Seems to have inferior OS
Scagliotti et al. 2015 (MARQUEE)	2011-01 to 2012-07	Phase 3 (C)	Erlotinib & Tivantinib	Did not meet primary endpoint of OS
Yoshioka et al. 2015 (ATTENTION)	2011-08 to 2012-10	Phase 3 (C)	Erlotinib & Tivantinib	Did not meet primary endpoint of OS
Ramalingam et al. 2014 (ARCHER 1009)	2011-2013	Phase 3 (C)	Dacomitinib	Did not meet primary endpoint of PFS
Cicènas et al. 2016 (IUNO)	2011-2014	Phase 3 (E-switch-ic)	See link	See link
Gridelli et al. 2018 (AvaALL)	2011-2015	Phase 3 (C)	Investigator's choice of: 1a. Docetaxel & Bevacizumab 1b. Erlotinib & Bevacizumab 1c. Pemetrexed & Bevacizumab	Did not meet primary endpoint of OS
Spigel et al. 2016 (METLung)	2012-01 to 2013-08	Phase 3 (C)	Erlotinib & Onartuzumab	Might have superior OS
Soria et al. 2015 (LUX-Lung 8)	2012-2014	Phase 3 (C)	Afatinib	Seems to have inferior OS¹
Neal et al. 2016 (ECOG-ACRIN 1512)	2013-2014	Randomized Phase 2 (C)	1. Cabozantinib	Inferior PFS
Neal et al. 2016 (ECOG-ACRIN 1512)	2013-2014	Randomized Phase 2 (C)	2. Cabozantinib & Erlotinib	Inferior PFS
Goldman et al. 2020 (JUNIPER)	2014-2017	Phase 3 (C)	Abemaciclib	Did not meet primary endpoint of OS

¹Reported efficacy is based on the 2021 update.
Note: the trials included here did not require EGFR mutation as a condition for enrollment. Given the FDA limitation on use in this setting issued in 2016, these regimens have been moved to the historical page. Note that there is another trial named TAILOR in colorectal cancer and another trial named DELTA in indolent lymphoma.

Biomarker eligibility criteria

JUNIPER: KRAS G12 or G13 mutation

Targeted therapy

Erlotinib (Tarceva) 150 mg PO once per day on days 1 to 28

28-day cycles

References

NCIC-CTG BR.21: Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00036647
ZEST: Natale RB, Thongprasert S, Greco FA, Thomas M, Tsai CM, Sunpaweravong P, Ferry D, Mulatero C, Whorf R, Thompson J, Barlesi F, Langmuir P, Gogov S, Rowbottom JA, Goss GD. Phase III trial of vandetanib compared with erlotinib in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol. 2011 Mar 10;29(8):1059-66. Epub 2011 Jan 31. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00364351
1. Dataset: Project Data Sphere
BeTa: Herbst RS, Ansari R, Bustin F, Flynn P, Hart L, Otterson GA, Vlahovic G, Soh CH, O'Connor P, Hainsworth J. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. Lancet. 2011 May 28;377(9780):1846-54. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed NCT00130728
TITAN: Ciuleanu T, Stelmakh L, Cicenas S, Miliauskas S, Grigorescu AC, Hillenbach C, Johannsdottir HK, Klughammer B, Gonzalez EE. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol. 2012 Mar;13(3):300-8. Epub 2012 Jan 24. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00556322
SUN 1087: Scagliotti GV, Krzakowski M, Szczesna A, Strausz J, Makhson A, Reck M, Wierzbicki RF, Albert I, Thomas M, Miziara JE, Papai ZS, Karaseva N, Thongprasert S, Portulas ED, von Pawel J, Zhang K, Selaru P, Tye L, Chao RC, Govindan R. Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer: a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2070-8. Epub 2012 May 7. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00457392
A7471028: Ramalingam SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, Seog Heo D, Rosell R, Talbot DC, Frank R, Letrent SP, Ruiz-Garcia A, Taylor I, Liang JQ, Campbell AK, O'Connell J, Boyer M. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2012 Sep 20;30(27):3337-44. Epub 2012 Jul 2. link to original article link to PMC article PubMed NCT00769067
CT/06.05: Karampeazis A, Voutsina A, Souglakos J, Kentepozidis N, Giassas S, Christofillakis C, Kotsakis A, Papakotoulas P, Rapti A, Agelidou M, Agelaki S, Vamvakas L, Samonis G, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Pemetrexed versus erlotinib in pretreated patients with advanced non-small cell lung cancer: a Hellenic Oncology Research Group (HORG) randomized phase 3 study. Cancer. 2013 Aug 1;119(15):2754-64. Epub 2013 May 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00440414
TAILOR_NSCLC: Garassino MC, Martelli O, Broggini M, Farina G, Veronese S, Rulli E, Bianchi F, Bettini A, Longo F, Moscetti L, Tomirotti M, Marabese M, Ganzinelli M, Lauricella C, Labianca R, Floriani I, Giaccone G, Torri V, Scanni A, Marsoni S; TAILOR trialists. Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol. 2013 Sep;14(10):981-8. Epub 2013 Jul 22. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00637910
DELTA_NSCLC: Kawaguchi T, Ando M, Asami K, Okano Y, Fukuda M, Nakagawa H, Ibata H, Kozuki T, Endo T, Tamura A, Kamimura M, Sakamoto K, Yoshimi M, Soejima Y, Tomizawa Y, Isa S, Takada M, Saka H, Kubo A. Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol. 2014 Jun 20;32(18):1902-8. Epub 2014 May 19. link to original article dosing details in manuscript have been reviewed by our editors PubMed
ARCHER 1009: Ramalingam SS, Jänne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. Epub 2014 Oct 15.link to original article PubMed NCT01360554
ADVIGO 1018: Scagliotti GV, Bondarenko I, Blackhall F, Barlesi F, Hsia TC, Jassem J, Milanowski J, Popat S, Sanchez-Torres JM, Novello S, Benner RJ, Green S, Molpus K, Soria JC, Shepherd FA. Randomized, phase III trial of figitumumab in combination with erlotinib versus erlotinib alone in patients with nonadenocarcinoma nonsmall-cell lung cancer. Ann Oncol. 2015 Mar;26(3):497-504. Epub 2014 Nov 13. link to original article PubMed NCT00673049
LUX-Lung 8: Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015 Aug;16(8):897-907. Epub 2015 Jul 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01523587
1. PRO analysis: Felip E, Hirsh V, Popat S, Cobo M, Fülöp A, Dayen C, Trigo JM, Gregg R, Waller CF, Soria JC, Goss GD, Gordon J, Wang B, Palmer M, Ehrnrooth E, Gadgeel SM. Symptom and Quality of Life Improvement in LUX-Lung 8, an Open-Label Phase III Study of Second-Line Afatinib Versus Erlotinib in Patients With Advanced Squamous Cell Carcinoma of the Lung After First-Line Platinum-Based Chemotherapy. Clin Lung Cancer. 2018 Jan;19(1):74-83.e11. Epub 2017 Jun 23. link to original article PubMed
2. Update: Goss GD, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Isla D, Morabito A, Min YJ, Ardizzoni A, Bender S, Cseh A, Felip E. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung: Final analysis of the randomised phase 3 LUX-Lung 8 trial. EClinicalMedicine. 2021 Jun 18;37:100940. link to original article link to PMC article PubMed
ATTENTION: Yoshioka H, Azuma K, Yamamoto N, Takahashi T, Nishio M, Katakami N, Ahn MJ, Hirashima T, Maemondo M, Kim SW, Kurosaki M, Akinaga S, Park K, Tsai CM, Tamura T, Mitsudomi T, Nakagawa K. A randomized, double-blind, placebo-controlled, phase III trial of erlotinib with or without a c-Met inhibitor tivantinib (ARQ 197) in Asian patients with previously treated stage IIIB/IV nonsquamous nonsmall-cell lung cancer harboring wild-type epidermal growth factor receptor (ATTENTION study). Ann Oncol. 2015 Oct;26(10):2066-72. Epub 2015 Jul 7. link to original article PubMed NCT01377376
MARQUEE: Scagliotti G, von Pawel J, Novello S, Ramlau R, Favaretto A, Barlesi F, Akerley W, Orlov S, Santoro A, Spigel D, Hirsh V, Shepherd FA, Sequist LV, Sandler A, Ross JS, Wang Q, von Roemeling R, Shuster D, Schwartz B. Phase III multinational, randomized, double-blind, placebo-controlled study of tivantinib (ARQ 197) plus erlotinib versus erlotinib alone in previously treated patients with locally advanced or metastatic nonsquamous non-small-cell lung cancer. J Clin Oncol. 2015 Aug 20;33(24):2667-74. Epub 2015 Jul 13. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01244191
WJOG 5108L: Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, Satouchi M, Iwamoto Y, Kanehara M, Fujimoto D, Ikeda N, Murakami H, Daga H, Oguri T, Goto I, Imamura F, Sugawara S, Saka H, Nogami N, Negoro S, Nakagawa K, Nakanishi Y. Randomized phase III study comparing gefitinib with erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016 Sep 20;34(27):3248-57. Epub 2016 Mar 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000002014
CurrentS: Smit EF, Wu YL, Gervais R, Zhou C, Felip E, Feng J, Guclu SZ, Hoiczyk M, Dorokhova E, Freudensprung U, Grange S, Perez-Moreno PD, Mitchell L, Reck M. A randomized, double-blind, phase III study comparing two doses of erlotinib for second-line treatment of current smokers with advanced non-small-cell lung cancer (CurrentS). Lung Cancer. 2016 Sep;99:94-101. Epub 2016 Jun 27. link to original article PubMed NCT01183858
IUNO: Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01328951
ECOG-ACRIN 1512: Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. Epub 2016 Nov 4. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT01708954
METLung: Spigel DR, Edelman MJ, O'Byrne K, Paz-Ares L, Mocci S, Phan S, Shames DS, Smith D, Yu W, Paton VE, Mok T. Results from the phase III randomized trial of onartuzumab plus erlotinib versus erlotinib in previously treated stage IIIB or IV non-small-cell lung cancer: METLung. J Clin Oncol. 2017 Feb;35(4):412-420. Epub 2016 Dec 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01456325
Wang Y, Wang H, Jiang Y, Zhang Y, Wang X. A randomized phase III study of combining erlotinib with bevacizumab and panitumumab versus erlotinib alone as second-line therapy for Chinese patients with non-small-cell lung cancer. Biomed Pharmacother. 2017 May;89:875-879. Epub 2017 Mar 6. link to original article PubMed
AvaALL: Gridelli C, de Castro Carpeno J, Dingemans AC, Griesinger F, Grossi F, Langer C, Ohe Y, Syrigos K, Thatcher N, Das-Gupta A, Truman M, Donica M, Smoljanovic V, Bennouna J. Safety and Efficacy of Bevacizumab Plus Standard-of-Care Treatment Beyond Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer: The AvaALL Randomized Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):e183486. Epub 2018 Dec 13. Erratum in: JAMA Oncol. 2018 Dec 1;4(12):1792. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed NCT01351415
JUNIPER: Goldman JW, Mazieres J, Barlesi F, Dragnev KH, Koczywas M, Göskel T, Cortot AB, Girard N, Wesseler C, Bischoff H, Nadal E, Park K, Lu S, Taus A, Cobo M, Estrem ST, Wijayawardana SR, Turner K, Oakley GJ 3rd, Hurt KC, Chiang AY, Hossain AM, John WJ, Paz-Ares L. A Randomized Phase III Study of Abemaciclib Versus Erlotinib in Patients with Stage IV Non-small Cell Lung Cancer With a Detectable KRAS Mutation Who Failed Prior Platinum-Based Therapy: JUNIPER. Front Oncol. 2020 Oct 26;10:578756. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02152631
WJOG5108LFS: Katakami N, Yokoyama T, Morita S, Okamoto T, Urata Y, Hattori Y, Iwamoto Y, Sato Y, Ikeda N, Takahashi T, Daga H, Oguri T, Fujisaka Y, Nishino K, Sugawara S, Kozuki T, Oki M, Yamamoto N, Nakagawa K. Overall survival analysis of patients enrolled in a randomized phase III trial comparing gefitinib and erlotinib for previously treated advanced lung adenocarcinoma (WJOG5108LFS). Int J Clin Oncol. 2023 Jan;28(1):79-88. Epub 2022 Nov 21. link to original article PubMed UMIN000002014

@@ Line 1: / Line 1: @@
-The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Non-small_cell_lung_cancer|main NSCLC page]] for current regimens.
+<span id="BackToTop"></span>
+<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
+[[#top|Back to Top]]
+</div>
+The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the [[Non-small_cell_lung_cancer|main NSCLC page]] for current regimens.
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
@@ Line 6: / Line 9: @@
 <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 |}
 {{TOC limit|limit=3}}
 =Neoadjuvant therapy=
 ==MIC {{#subobject:6be6b3|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 MIC: '''<u>M</u>'''itomycin, '''<u>I</u>'''fosfamide, '''<u>C</u>'''isplatin
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:c1b1e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJM199401203300301 Rosell et al. 1994]
+|[https://doi.org/10.1056/NEJM199401203300301 Rosell et al. 1994]
 |1989-1991
-|style="background-color:#1a9851"|Phase III (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-esc)
 |[[Non-small_cell_lung_cancer_-_null_regimens#No_neoadjuvant_therapy|No preoperative therapy]]
 | style="background-color:#1a9850" |Superior OS
@@ Line 31: / Line 30: @@
 |[https://doi.org/10.1200/JCO.2002.20.1.247 Depierre et al. 2002]
 |1991-1997
-|style="background-color:#1a9851"|Phase III (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-esc)
 |[[Non-small_cell_lung_cancer_-_null_regimens#No_neoadjuvant_therapy|No preoperative therapy]]
-| style="background-color:#ffffbf" |Seems not superior
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Mitomycin (Mutamycin)]] 6 mg/m<sup>2</sup> IV once on day 1
 *[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1
 *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-====Supportive medications====
+====Supportive therapy====
 *[[Mesna (Mesnex)]] 1000 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''admixed with ifosfamide'''
 *[[Metoclopramide (Reglan)]] 3 mg/kg IV, given 30 minutes prior and 90 minutes after chemotherapy
 *[[Dexamethasone (Decadron)]] 20 mg IV once, given 30 minutes prior to chemotherapy
 '''21-day cycle for 3 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *[[Surgery#Lung_cancer_surgery|Surgery]]
+</div></div>
 ===References===
-# Rosell R, Gómez-Codina J, Camps C, Maestre J, Padille J, Cantó A, Mate JL, Li S, Roig J, Olazábal A, Canela M, Ariza A, Skacel Z, Morera-Prat J, Abad A. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med. 1994 Jan 20;330(3):153-8. [https://www.nejm.org/doi/full/10.1056/NEJM199401203300301 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/8043059 PubMed]
+# Rosell R, Gómez-Codina J, Camps C, Maestre J, Padille J, Cantó A, Mate JL, Li S, Roig J, Olazábal A, Canela M, Ariza A, Skacel Z, Morera-Prat J, Abad A. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med. 1994 Jan 20;330(3):153-8. [https://doi.org/10.1056/NEJM199401203300301 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8043059/ PubMed]
-# Depierre A, Milleron B, Moro-Sibilot D, Chevret S, Quoix E, Lebeau B, Braun D, Breton JL, Lemarié E, Gouva S, Paillot N, Bréchot JM, Janicot H, Lebas FX, Terrioux P, Clavier J, Foucher P, Monchâtre M, Coëtmeur D, Level MC, Leclerc P, Blanchon F, Rodier JM, Thiberville L, Villeneuve A, Westeel V, Chastang C; IFCT. Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. J Clin Oncol. 2002 Jan 1;20(1):247-53. [https://doi.org/10.1200/JCO.2002.20.1.247 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11773176 PubMed]
+# Depierre A, Milleron B, Moro-Sibilot D, Chevret S, Quoix E, Lebeau B, Braun D, Breton JL, Lemarié E, Gouva S, Paillot N, Bréchot JM, Janicot H, Lebas FX, Terrioux P, Clavier J, Foucher P, Monchâtre M, Coëtmeur D, Level MC, Leclerc P, Blanchon F, Rodier JM, Thiberville L, Villeneuve A, Westeel V, Chastang C; IFCT. Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. J Clin Oncol. 2002 Jan 1;20(1):247-53. [https://doi.org/10.1200/JCO.2002.20.1.247 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11773176/ PubMed]
 =Adjuvant therapy=
 ==Radiation therapy {{#subobject:743aa8|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:426dfc|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 69: / Line 67: @@
 |[https://doi.org/10.1056/nejm200010263431703 Keller et al. 2000 (ECOG E3590)]
 |1991-1997
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|EP & RT
+|[[#Cisplatin_.26_Etoposide_.28EP.29_.26_RT|EP & RT]]
-|style="background-color:#ffffbf"|Seems not superior
+|style="background-color:#ffffbf"|Did not meet endpoint of OS
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *Complete [[Surgery#Lung_cancer_surgery|surgical resection]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Radiotherapy====
-*[[External_beam_radiotherapy|Radiation therapy]], 1.8 Gy fractions x 28 fractions (total dose: 50.4 Gy)
+*[[External_beam_radiotherapy|Radiation therapy]], 180 cGy fractions x 28 fractions (total dose: 5040 cGy)
 '''5-week course'''
+</div></div>
 ===References===
-# '''ECOG E3590:''' Keller SM, Adak S, Wagner H, Herskovic A, Komaki R, Brooks BJ, Perry MC, Livingston RB, Johnson DH; [[Study_Groups#ECOG|ECOG]]. A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer. N Engl J Med. 2000 Oct 26;343(17):1217-22. [https://doi.org/10.1056/nejm200010263431703 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/11071672 PubMed]
+# '''ECOG E3590:''' Keller SM, Adak S, Wagner H, Herskovic A, Komaki R, Brooks BJ, Perry MC, Livingston RB, Johnson DH; [[Study_Groups#ECOG|ECOG]]. A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer. N Engl J Med. 2000 Oct 26;343(17):1217-22. [https://doi.org/10.1056/nejm200010263431703 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11071672/ PubMed]
 =Induction therapy for locally advanced disease=
 ==MIC {{#subobject:ebf0c1|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 MIC: '''<u>M</u>'''itomycin, '''<u>I</u>'''fosfamide, '''<u>C</u>'''isplatin
 <br>MIP: '''<u>M</u>'''itomycin, '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:d1267e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 102: / Line 98: @@
 |[https://doi.org/10.1023/a:1008319506107 Sculier et al. 1999]
 |1989-1996
-| style="background-color:#91cf61" |Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
@@ Line 108: / Line 104: @@
 |[https://doi.org/10.1093/annonc/mdh105 Sculier et al. 2004]
 |1996-2002
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|SuperMIP
+|[[#SuperMIP_999|SuperMIP]]
-| style="background-color:#ffffbf" |Seems not superior
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Mitomycin (Mutamycin)]]
+*[[Mitomycin (Mutamycin)]] 6 mg/m<sup>2</sup> IV bolus once on day 1, '''given first'''
-*[[Ifosfamide (Ifex)]]
+*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given second'''
-*[[Cisplatin (Platinol)]]
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given third, 3 hours after the end of ifosfamide infusion'''
+====Supportive therapy====
+*[[Mesna (Mesnex)]] 1000 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given with ifosfamide''', then 500 mg/m<sup>2</sup> IV bolus at four and eight hours after ifosfamide
+*[[Lorazepam (Ativan)]]
+*[[Metoclopramide (Reglan)]]
+*[[Dexamethasone (Decadron)]]
+'''21- to 28-day cycle for 3 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
-*Sculier et al. 1999: MIP x 3 versus [[Non-small_cell_lung_cancer#Radiation_therapy|RT]]
+*Sculier et al. 1999: [[#MIC|MIP]] continuation x 3 versus [[Non-small_cell_lung_cancer#Radiation_therapy|RT]] consolidation
-*Sculier et al. 2004: [[Non-small_cell_lung_cancer#Radiation_therapy|RT]]
+*Sculier et al. 2004: [[Non-small_cell_lung_cancer#Radiation_therapy|RT]] consolidation
+</div></div>
 ===References===
-# Sculier JP, Paesmans M, Lafitte JJ, Baumöhl J, Thiriaux J, van Cutsem O, Recloux P, Bureau G, Berchier MC, Zacharias C, Mommen P, Bosschaerts T, Berghmans T, van Houtte P, Ninane V, Klastersky J; European Lung Cancer Working Party. A randomised phase III trial comparing consolidation treatment with further chemotherapy to chest irradiation in patients with initially unresectable locoregional non-small-cell lung cancer responding to induction chemotherapy. Ann Oncol. 1999 Mar;10(3):295-303. [https://doi.org/10.1023/a:1008319506107 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10355573 PubMed]
+# Sculier JP, Paesmans M, Lafitte JJ, Baumöhl J, Thiriaux J, van Cutsem O, Recloux P, Bureau G, Berchier MC, Zacharias C, Mommen P, Bosschaerts T, Berghmans T, van Houtte P, Ninane V, Klastersky J; European Lung Cancer Working Party. A randomised phase III trial comparing consolidation treatment with further chemotherapy to chest irradiation in patients with initially unresectable locoregional non-small-cell lung cancer responding to induction chemotherapy. Ann Oncol. 1999 Mar;10(3):295-303. [https://doi.org/10.1023/a:1008319506107 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10355573/ PubMed]
-# Sculier JP, Lafitte JJ, Berghmans T, Van Houtte P, Lecomte J, Thiriaux J, Efremidis A, Koumakis G, Giner V, Richez M, Corhay JL, Wackenier P, Lothaire P, Paesmans M, Mommen P, Ninane V; European Lung Cancer Working Party. A phase III randomised study comparing two different dose-intensity regimens as induction chemotherapy followed by thoracic irradiation in patients with advanced locoregional non-small-cell lung cancer. Ann Oncol. 2004 Mar;15(3):399-409. [https://doi.org/10.1093/annonc/mdh105 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14998841 PubMed]
+# Sculier JP, Lafitte JJ, Berghmans T, Van Houtte P, Lecomte J, Thiriaux J, Efremidis A, Koumakis G, Giner V, Richez M, Corhay JL, Wackenier P, Lothaire P, Paesmans M, Mommen P, Ninane V; European Lung Cancer Working Party. A phase III randomised study comparing two different dose-intensity regimens as induction chemotherapy followed by thoracic irradiation in patients with advanced locoregional non-small-cell lung cancer. Ann Oncol. 2004 Mar;15(3):399-409. [https://doi.org/10.1093/annonc/mdh105 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/14998841/ PubMed]
 ==PEV {{#subobject:ebf0c1|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 PEV: '''<u>P</u>'''latinol (Cisplatin), '''<u>E</u>'''toposide, '''<u>V</u>'''inblastine
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:d1267e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://insights.ovid.com/pubmed?pmid=12040280 Kim et al. 2002]
+|[https://doi.org/10.1097/00000421-200206000-00007 Kim et al. 2002]
 |1988-1992
-|style="background-color:#1a9851"|Phase III (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-esc)
-|[[Non-small_cell_lung_cancer_-_null_regimens#No_induction|No induction]]
+|[[Non-small_cell_lung_cancer_-_null_regimens#No_induction|No induction chemotherapy]]
-| style="background-color:#ffffbf" |Seems not superior
+| style="background-color:#d9ef8b" |Might have superior OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]]
+*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
-*[[Etoposide (Vepesid)]]
+*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 2 to 4
-*[[Vinblastine (Velban)]]
+*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 3 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
-*[[Non-small_cell_lung_cancer#Radiation_therapy|RT]]
+*[[Non-small_cell_lung_cancer#Radiation_therapy|RT]] consolidation
+</div></div>
 ===References===
-# Kim TY, Yang SH, Lee SH, Park YS, Im YH, Kang WK, Ha SH, Park CI, Heo DS, Bang YJ, Kim NK. A phase III randomized trial of combined chemoradiotherapy versus radiotherapy alone in locally advanced non-small-cell lung cancer. Am J Clin Oncol. 2002 Jun;25(3):238-43. [https://insights.ovid.com/pubmed?pmid=12040280 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12040280 PubMed]
+# Kim TY, Yang SH, Lee SH, Park YS, Im YH, Kang WK, Ha SH, Park CI, Heo DS, Bang YJ, Kim NK. A phase III randomized trial of combined chemoradiotherapy versus radiotherapy alone in locally advanced non-small-cell lung cancer. Am J Clin Oncol. 2002 Jun;25(3):238-43. [https://doi.org/10.1097/00000421-200206000-00007 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12040280/ PubMed]
 =Definitive therapy for locally advanced disease=
 ==MVP & RT {{#subobject:10d15d|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 MVP & RT: '''<u>M</u>'''itomycin, '''<u>V</u>'''indesine, '''<u>P</u>'''latinol (Cisplatin), '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen {{#subobject:8fd069|Variant=1}}===
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #1 {{#subobject:8fd069|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 172: / Line 175: @@
 |[https://doi.org/10.1200/JCO.1999.17.9.2692 Furuse et al. 1999 (JCOG9202)]
 |1992-1994
-|style="background-color:#1a9851"|Phase III (E-switch-ic)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
-|MVP, then RT
+|[[#MVP_.28Vindesine.29_888|MVP]], then [[#Radiation_therapy_888|RT]]
 | style="background-color:#91cf60" |Seems to have superior OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Mitomycin (Mutamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 1 & 29
+*[[Vindesine (Eldisine)]] 3 mg/m<sup>2</sup> IV once per day on days 1, 8, 29, 36
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once per day on days 1 & 29
+====Radiotherapy====
+*Concurrent [[External beam radiotherapy]] 5600 cGy in 28 fractions, given on days 1 to 5, 8 to 12, 15 to 19, 29 to 33, 36 to 40, 43 to 46
+'''46-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #2 {{#subobject:8fd081|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.2009.24.5050 Yamamoto et al. 2010 (WJTOG0105)]
+|2001-2005
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_.28CP.29_.26_RT|CP & RT]]<br>2. [[#Carboplatin.2C_Irinotecan.2C_RT_999|Carboplatin, Irinotecan, RT]]
+| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS (primary endpoint)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Mitomycin (Mutamycin)]]
+*[[Mitomycin (Mutamycin)]] 8 mg/m<sup>2</sup> IV once on day 1
-*[[Vindesine (Eldisine)]]
+*[[Vindesine (Eldisine)]] 3 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Cisplatin (Platinol)]]
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 ====Radiotherapy====
-*[[External beam radiotherapy]]
+*Concurrent [[External beam radiotherapy]] as follows (total dose 6000 cGy):
+**Cycles 1 & 3: 200 cGy per fraction x 15 fractions, given on days 2 to 6, 9 to 13, 16 to 20
+'''28-day cycle for 4 cycles'''
+</div></div>
 ===References===
-# '''JCOG9202:''' Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, Katagami N, Ariyoshi Y. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999 Sep;17(9):2692-9. [https://doi.org/10.1200/JCO.1999.17.9.2692 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10561343 PubMed]
+# '''JCOG9202:''' Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, Katagami N, Ariyoshi Y. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999 Sep;17(9):2692-9. [https://doi.org/10.1200/JCO.1999.17.9.2692 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10561343/ PubMed]
+#'''WJTOG0105:''' Yamamoto N, Nakagawa K, Nishimura Y, Tsujino K, Satouchi M, Kudo S, Hida T, Kawahara M, Takeda K, Katakami N, Sawa T, Yokota S, Seto T, Imamura F, Saka H, Iwamoto Y, Semba H, Chiba Y, Uejima H, Fukuoka M. Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer: West Japan Thoracic Oncology Group WJTOG0105. J Clin Oncol. 2010 Aug 10;28(23):3739-45. Epub 2010 Jul 12. [https://doi.org/10.1200/JCO.2009.24.5050 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20625120/ PubMed] [https://clinicaltrials.gov/study/NCT00144053 NCT00144053]
+##'''Update:''' Zenke Y, Tsuboi M, Chiba Y, Tsujino K, Satouchi M, Sawa K, Shimizu J, Daga H, Fujimoto D, Mori M, Aoki T, Sawa T, Omori S, Saka H, Iwamoto Y, Okuno M, Hirashima T, Kashiwabara K, Tachihara M, Yamamoto N, Nakagawa K. Effect of Second-generation vs Third-generation Chemotherapy Regimens With Thoracic Radiotherapy on Unresectable Stage III Non-Small-Cell Lung Cancer: 10-Year Follow-up of a WJTOG0105 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Jun 1;7(6):904-909. [https://doi.org/10.1001/jamaoncol.2021.0113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7974833/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33734289/ PubMed]
-=Consolidation or maintenance after definitive therapy for inoperable disease=
+=Maintenance after definitive therapy for inoperable disease=
+==BCG vaccine monotherapy==
-==Bacillus Calmette-Guérin (BCG) monotherapy==
+<div class="toccolours" style="background-color:#ee6b6e">
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 ===Regimen===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(76)90213-0/fulltext Pines 1976]
+|[https://doi.org/10.1016/S0140-6736(76)90213-0 Pines 1976]
 |1970-1973
-|style="background-color:#1a9851"|Randomized (C)
+|style="background-color:#1a9851"|Randomized (E-esc)
 |[[Non-small_cell_lung_cancer#Observation_2|Observation]]
 | style="background-color:#91cf60" |Seems to have superior OS
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*RT
+*[[Regimen_classes#Radiotherapy-based_regimen|RT]] consolidation
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
-*[[Bacillus Calmette-Guérin (BCG)]]
+*[[BCG vaccine]]
+</div></div>
 ===References===
-# Pines A. A 5-year controlled study of BCG and radiotherapy inoperable lung cancer. Lancet. 1976 Feb 21;1(7956):380-1. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(76)90213-0/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/55647 PubMed]
+# Pines A. A 5-year controlled study of BCG and radiotherapy inoperable lung cancer. Lancet. 1976 Feb 21;1(7956):380-1. [https://doi.org/10.1016/S0140-6736(76)90213-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/55647/ PubMed]
 =Advanced or metastatic disease, first-line=
 ==CAMP {{#subobject:2d62ce|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 CAMP: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rocarbazine
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:f79237|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 20%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://jamanetwork.com/journals/jama/article-abstract/362874 Bitran et al. 1978]
+|[https://doi.org/10.1001/jama.1978.03290250047027 Bitran et al. 1978]
+|1975-1977
 | style="background-color:#91cf61" |Non-randomized
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1200/JCO.1986.4.1.14 Ruckdeschel et al. 1986 (ECOG E1581)]
+|1981-1983
+| style="background-color:#1a9851" |Randomized (E-esc)
+|1. [[#MVP_.28Vinblastine.29|MVP]]<br>2. [[Non-small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_3|EC]]<br> 3. [[#Cisplatin_.26_Vindesine|VC]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
+*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV push once per day on days 1 & 8
-*[[Doxorubicin (Adriamycin)]]
+*[[Doxorubicin (Adriamycin)]] 20 mg/m<sup>2</sup> IV push once per day on days 1 & 8 (maximum cumulative dose of 450 mg/m<sup>2</sup>)
-*[[Methotrexate (MTX)]]
+*[[Methotrexate (MTX)]] 15 mg/m<sup>2</sup> IV push once per day on days 1 & 8
-*[[Procarbazine (Matulane)]]
+*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 10 or days 2 to 11
+'''28-day cycles'''
+</div></div>
 ===References===
-# Bitran JD, Desser RK, DeMeester T, Golomb HM. Metastatic non-oat-cell bronchogenic carcinoma: therapy with cyclophosphamide, doxorubicin, methotrexate, and procarbazine (CAMP). JAMA. 1978 Dec 15;240(25):2743-6. [https://jamanetwork.com/journals/jama/article-abstract/362874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/713008 PubMed]
+# Bitran JD, Desser RK, DeMeester T, Golomb HM. Metastatic non-oat-cell bronchogenic carcinoma: therapy with cyclophosphamide, doxorubicin, methotrexate, and procarbazine (CAMP). JAMA. 1978 Dec 15;240(25):2743-6. [https://doi.org/10.1001/jama.1978.03290250047027 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/713008/ PubMed]
-# '''ECOG E1581:''' Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. [https://doi.org/10.1200/JCO.1986.4.1.14 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3510278 PubMed]
+# '''ECOG E1581:''' Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. [https://doi.org/10.1200/JCO.1986.4.1.14 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/3510278/ PubMed]
-==CAP (Platinol) {{#subobject:379e5f|Regimen=1}}==
+==Carboplatin & Cisplatin {{#subobject:a0e2a9|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+CC: '''<u>C</u>'''isplatin & '''<u>C</u>'''arboplatin
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen {{#subobject:e1bc46|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1998.16.4.1388 Sculier et al. 1998]
+|1990-1995
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#CCI|CCI]]
+| style="background-color:#d73027" |Inferior ORR
 |-
-|[[#top|back to top]]
 |}
-CAP: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''latinol (Cisplatin)
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] 200 mg/m<sup>2</sup> IV over 30 minutes once on day 1
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV over 15 minutes once per day on days 2 & 3
+'''21- to 28-day cycles'''
+</div></div>
+===References===
+# Sculier JP, Paesmans M, Thiriaux J, Lecomte J, Bureau G, Giner V, Efremidis A, Lafitte JJ, Berchier MC, Alexopoulos CG, Zacharias C, Mommen P, Ninane V, Klastersky J; European Lung Cancer Working Party. Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. J Clin Oncol. 1998 Apr;16(4):1388-96. [https://doi.org/10.1200/JCO.1998.16.4.1388 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9552042/ PubMed]
+==CCI {{#subobject:a0532c|Regimen=1}}==
+CCI: '''<u>C</u>'''isplatin, '''<u>C</u>'''arboplatin, '''<u>I</u>'''fosfamide
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #1 {{#subobject:ebjb16|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1093/annonc/mdf154 Sculier et al. 2002]
+|1998-2000
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[Stub#CCG|CCG]]<br>2. [[#Ifosfamide_.26_Gemcitabine|IG]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 3 IV over 30 minutes once on day 1, '''given second'''
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given third'''
+*[[Ifosfamide (Ifex)]] 4500 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
+====Supportive therapy====
+*[[Mesna (Mesnex)]]
+'''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #2 {{#subobject:ebgc16|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1998.16.4.1388 Sculier et al. 1998]
+|1990-1995
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[#Carboplatin_.26_Cisplatin|CC]]
+| style="background-color:#1a9850" |Superior ORR
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] 200 mg/m<sup>2</sup> IV over 30 minutes once on day 1, '''given first'''
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV over 15 minutes once per day on days 2 & 3, '''given first'''
+*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 3, '''given second'''
+====Supportive therapy====
+*[[Mesna (Mesnex)]] 300 mg/m<sup>2</sup> IV once prior to first dose of ifosfamide, then 300 mg/m<sup>2</sup> IV every 4 hours for 72 hours
+'''21- to 28-day cycles'''
+</div></div>
+===References===
+# Sculier JP, Paesmans M, Thiriaux J, Lecomte J, Bureau G, Giner V, Efremidis A, Lafitte JJ, Berchier MC, Alexopoulos CG, Zacharias C, Mommen P, Ninane V, Klastersky J; European Lung Cancer Working Party. Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. J Clin Oncol. 1998 Apr;16(4):1388-96. [https://doi.org/10.1200/JCO.1998.16.4.1388 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9552042/ PubMed]
+# Sculier JP, Lafitte JJ, Lecomte J, Berghmans T, Thiriaux J, Florin MC, Efremidis A, Alexopoulos CG, Recloux P, Ninane V, Mommen P, Paesmans M, Klastersky J; European Lung Cancer Working Party. A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer. Ann Oncol. 2002 Jun;13(6):874-82. [https://doi.org/10.1093/annonc/mdf154 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12123332/ PubMed]
+==CISCA {{#subobject:379e5f|Regimen=1}}==
+CISCA: '''<u>CIS</u>'''platin, '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin)
+<br>CAP: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''latinol (Cisplatin)
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:e7847b|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 257: / Line 385: @@
 |1978-1981
 | style="background-color:#1a9851" |Phase 3 (C)
-|1. Cyclophosphamide & Doxorubicin (AC)<br> 2. CAMF
+|1. [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_999|Cyclophosphamide & Doxorubicin (AC)]]<br>2. [[#CAMF_999|CAMF]]
 | style="background-color:#ffffbf" |Did not meet endpoint of OS
 |-
@@ Line 263: / Line 391: @@
 |1980-1983
 | style="background-color:#1a9851" |Phase 3 (C)
-|1. FOMi<br> 2. FOMi/CAP
+|1. [[#FOMi_888|FOMi]]<br>2. [[#FOMi.2FCAP_888|FOMi/CAP]]
 | style="background-color:#fc8d59" |Seems to have inferior OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once on day 1
 *[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
 *[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV once on day 1
 '''21-day cycles'''
+</div></div>
 ===References===
-# Robert F, Omura GA, Birch R, Krauss S, Oldham R; SECG. Randomized phase III comparison of three doxorubicin-based chemotherapy regimens in advanced non-small cell lung cancer: a Southeastern Cancer Study Group trial. J Clin Oncol. 1984 May;2(5):391-5. [https://doi.org/10.1200/jco.1984.2.5.391 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/6374050/ PubMed]
+# Robert F, Omura GA, Birch R, Krauss S, Oldham R; SECG. Randomized phase III comparison of three doxorubicin-based chemotherapy regimens in advanced non-small cell lung cancer: a Southeastern Cancer Study Group trial. J Clin Oncol. 1984 May;2(5):391-5. [https://doi.org/10.1200/jco.1984.2.5.391 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/6374050/ PubMed]
-# '''SWOG S8012:''' Miller TP, Chen TT, Coltman CA Jr, O'Bryan RM, Vance RB, Weiss GB, Fletcher WS, Stephens RL, Livingston RB. Effect of alternating combination chemotherapy on survival of ambulatory patients with metastatic large-cell and adenocarcinoma of the lung: a Southwest Oncology Group Study. J Clin Oncol. 1986 Apr;4(4):502-8. [https://doi.org/10.1200/JCO.1986.4.4.502 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3007683 PubMed]
+# '''SWOG S8012:''' Miller TP, Chen TT, Coltman CA Jr, O'Bryan RM, Vance RB, Weiss GB, Fletcher WS, Stephens RL, Livingston RB. Effect of alternating combination chemotherapy on survival of ambulatory patients with metastatic large-cell and adenocarcinoma of the lung: a Southwest Oncology Group Study. J Clin Oncol. 1986 Apr;4(4):502-8. [https://doi.org/10.1200/JCO.1986.4.4.502 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3007683/ PubMed]
+==Cisplatin monotherapy {{#subobject:a0eb49|Regimen=1}}==
-==Carboplatin & Cisplatin {{#subobject:a0e2a9|Regimen=1}}==
+<div class="toccolours" style="background-color:#ee6b6e">
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Regimen variant #1, 75 q3wk x 8 {{#subobject:e32b48|Variant=1}}===
-|-
-|[[#top|back to top]]
-|}
-CC: '''<u>C</u>'''isplatin & '''<u>C</u>'''arboplatin
-===Regimen {{#subobject:e1bc46|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.1998.16.4.1388 Sculier et al. 1998]
+|[https://doi.org/10.1200/JCO.2000.18.6.1351 von Pawel et al. 2000 (CATAPULT I)]
-|1990-1995
+|Not reported
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|[[#CCI|CCI]]
+|[[#Cisplatin_.26_Tirapazamine_777|Cisplatin & Tirapazamine]]
-| style="background-color:#d73027" |Inferior ORR
+| style="background-color:#d73027" |Inferior OS
 |-
 |}
-''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]]
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
-*[[Cisplatin (Platinol)]]
+'''21-day cycle for up to 8 cycles'''
+</div></div><br>
-===References===
+<div class="toccolours" style="background-color:#ee6b6e">
-# Sculier JP, Paesmans M, Thiriaux J, Lecomte J, Bureau G, Giner V, Efremidis A, Lafitte JJ, Berchier MC, Alexopoulos CG, Zacharias C, Mommen P, Ninane V, Klastersky J; European Lung Cancer Working Party. Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. J Clin Oncol. 1998 Apr;16(4):1388-96. [https://doi.org/10.1200/JCO.1998.16.4.1388 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9552042 PubMed]
+===Regimen variant #2, 100 q3wk {{#subobject:e33346|Variant=1}}===
-==CCI {{#subobject:a0532c|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-CCI: '''<u>C</u>'''isplatin, '''<u>C</u>'''arboplatin, '''<u>I</u>'''fosfamide
-===Regimen {{#subobject:ebjb16|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.1998.16.4.1388 Sculier et al. 1998]
+|[https://doi.org/10.1200/JCO.2000.18.19.3390 Gatzemeier et al. 2000]
-|1990-1995
+|1995-01 to 1996-04
-|style="background-color:#1a9851"|Phase III (E-esc)
+|style="background-color:#1a9851"|Phase 3 (C)
-|[[#Carboplatin_.26_Cisplatin|CC]]
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
-| style="background-color:#1a9850" |Superior ORR
+| style="background-color:#fc8d59" |Seems to have inferior TTP
-|-
-|[https://doi.org/10.1093/annonc/mdf154 Sculier et al. 2002]
-|1998-2000
-|style="background-color:#1a9851"|Phase III (C)
-|1. [[Stub#CCG|CCG]]<br> 2. [[#Ifosfamide_.26_Gemcitabine|IG]]
-| style="background-color:#ffffbf" |Seems not superior
 |-
 |}
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]]
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 30 minutes once on day 1
-*[[Cisplatin (Platinol)]]
+'''21-day cycle for up to 6 cycles'''
-*[[Ifosfamide (Ifex)]]
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
-===References===
+===Regimen variant #3, 100 q4wk {{#subobject:e32b46|Variant=1}}===
-# Sculier JP, Paesmans M, Thiriaux J, Lecomte J, Bureau G, Giner V, Efremidis A, Lafitte JJ, Berchier MC, Alexopoulos CG, Zacharias C, Mommen P, Ninane V, Klastersky J; European Lung Cancer Working Party. Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. J Clin Oncol. 1998 Apr;16(4):1388-96. [https://doi.org/10.1200/JCO.1998.16.4.1388 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9552042 PubMed]
-# Sculier JP, Lafitte JJ, Lecomte J, Berghmans T, Thiriaux J, Florin MC, Efremidis A, Alexopoulos CG, Recloux P, Ninane V, Mommen P, Paesmans M, Klastersky J; European Lung Cancer Working Party. A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer. Ann Oncol. 2002 Jun;13(6):874-82. [https://doi.org/10.1093/annonc/mdf154 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12123332 PubMed]
-==Cisplatin monotherapy {{#subobject:a0eb49|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:e32b46|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 357: / Line 462: @@
 |[https://doi.org/10.1200/JCO.1993.11.5.873 Gandara et al. 1993]
 |1988-1990
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|1. HDCP<br> 2. HDCP-M
+|1. [[#Cisplatin_monotherapy_999|HDCP]]<br>2. [[#Cisplatin_.26_Mitomycin_999|HDCP-M]]
-| style="background-color:#ffffbf" |Seems not superior
+| style="background-color:#ffffbf" |Did not meet endpoint of OS
 |-
-|[https://doi.org/10.1200/JCO.2000.18.6.1351 von Pawel et al. 2000 (CATAPULT I)]
+|[https://doi.org/10.1200/JCO.1998.16.7.2459 Wozniak et al. 1998 (SWOG S9308)]
-|NR
+|1993-1995
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|Cisplatin & Tirapazamine
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine_.28CVb.29_3|CVb]]
 | style="background-color:#d73027" |Inferior OS
 |-
-|[https://doi.org/10.1200/JCO.2000.18.19.3390 Gatzemeier et al. 2000]
+|[https://doi.org/10.1200/JCO.2000.18.1.122 Sandler et al. 2000]
-|1995-1996
+|1995-1997
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[Non-small_cell_lung_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_.28GC.29_3|GC]]
-| style="background-color:#fc8d59" |Seems to have inferior TTP
+| style="background-color:#d73027" |Inferior OS
 |-
 |}
-''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]]
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 30 to 120 minutes once on day 1
+'''28-day cycle for 6 cycles (Sandler et al. 2000) or indefinitely'''
+</div></div>
 ===References===
-# Gandara DR, Crowley J, Livingston RB, Perez EA, Taylor CW, Weiss G, Neefe JR, Hutchins LF, Roach RW, Grunberg SM, Braun TJ, Natale RB, Balcerzak SP; [[Study_Groups#SWOG|SWOG]]. Evaluation of cisplatin intensity in metastatic non-small-cell lung cancer: a phase III study of the Southwest Oncology Group. J Clin Oncol. 1993 May;11(5):873-8. [https://doi.org/10.1200/JCO.1993.11.5.873 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8387576 PubMed]
+# Gandara DR, Crowley J, Livingston RB, Perez EA, Taylor CW, Weiss G, Neefe JR, Hutchins LF, Roach RW, Grunberg SM, Braun TJ, Natale RB, Balcerzak SP; [[Study_Groups#SWOG|SWOG]]. Evaluation of cisplatin intensity in metastatic non-small-cell lung cancer: a phase III study of the Southwest Oncology Group. J Clin Oncol. 1993 May;11(5):873-8. [https://doi.org/10.1200/JCO.1993.11.5.873 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8387576/ PubMed]
-# '''CATAPULT I:''' von Pawel J, von Roemeling R, Gatzemeier U, Boyer M, Elisson LO, Clark P, Talbot D, Rey A, Butler TW, Hirsh V, Olver I, Bergman B, Ayoub J, Richardson G, Dunlop D, Arcenas A, Vescio R, Viallet J, Treat J. Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group: cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors. J Clin Oncol. 2000 Mar;18(6):1351-9. [https://doi.org/10.1200/JCO.2000.18.6.1351 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/10715308 PubMed]
+#'''SWOG S9308:''' Wozniak AJ, Crowley JJ, Balcerzak SP, Weiss GR, Spiridonidis CH, Baker LH, Albain KS, Kelly K, Taylor SA, Gandara DR, Livingston RB; [[Study_Groups#SWOG|SWOG]]. Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. J Clin Oncol. 1998 Jul;16(7):2459-65. [https://doi.org/10.1200/JCO.1998.16.7.2459 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9667264/ PubMed]
-# Gatzemeier U, von Pawel J, Gottfried M, ten Velde GP, Mattson K, de Marinis F, Harper P, Salvati F, Robinet G, Lucenti A, Bogaerts J, Gallant G. Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Oct 1;18(19):3390-9. [https://doi.org/10.1200/JCO.2000.18.19.3390 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/11013280 PubMed]
+#Sandler AB, Nemunaitis J, Denham C, von Pawel J, Cormier Y, Gatzemeier U, Mattson K, Manegold C, Palmer MC, Gregor A, Nguyen B, Niyikiza C, Einhorn LH. Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2000 Jan;18(1):122-30. [https://doi.org/10.1200/JCO.2000.18.1.122 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10623702/ PubMed]
+# '''CATAPULT I:''' von Pawel J, von Roemeling R, Gatzemeier U, Boyer M, Elisson LO, Clark P, Talbot D, Rey A, Butler TW, Hirsh V, Olver I, Bergman B, Ayoub J, Richardson G, Dunlop D, Arcenas A, Vescio R, Viallet J, Treat J. Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group: cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors. J Clin Oncol. 2000 Mar;18(6):1351-9. [https://doi.org/10.1200/JCO.2000.18.6.1351 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10715308/ PubMed]
+# Gatzemeier U, von Pawel J, Gottfried M, ten Velde GP, Mattson K, de Marinis F, Harper P, Salvati F, Robinet G, Lucenti A, Bogaerts J, Gallant G. Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Oct 1;18(19):3390-9. [https://doi.org/10.1200/JCO.2000.18.19.3390 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11013280/ PubMed]
 ==Cisplatin & Pemetrexed {{#subobject:af12b4|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 Pem-Cis: '''<u>Pem</u>'''etrexed & '''<u>Cis</u>'''platin
 <br>Cis-Pem: '''<u>Cis</u>'''platin & '''<u>Pem</u>'''etrexed
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:8fdaa3|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 399: / Line 505: @@
 |-
 |[https://doi.org/10.1200/jco.2007.15.0375 Scagliotti et al. 2008 (JMDB)]
-|2004-2005
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-|style="background-color:#1a9851"|Phase III (E-RT-switch-ic)
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-66-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
+|-
+|} -->
+|2004-07 to 2005-12
+|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
 |[[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
-|style="background-color:#eeee01"|Seems non-inferior
+|style="background-color:#eeee01"|Seems to have non-inferior OS (primary endpoint)<br>Median OS: 10.3 vs 10.3 mo<br>(HR 0.94, 95% CI 0.84-1.05)
 |-
 |}
 ''Note: although this regimen is still current for nonsquamous NSCLC, the JMDB trial was unselected by histology.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1, '''given second'''
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
-*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1, '''given first'''
+*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV once on day 1
+====Supportive therapy====
-====Supportive medications====
+*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM every 9 weeks, first dose 1 to 2 weeks prior to pemetrexed
-*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM every 9 weeks, first dose prior to [[Pemetrexed (Alimta)]]
+*Folic acid 350 mcg to 1 mg PO once per day
-*Folic acid 1 mg PO once per day
+*[[Dexamethasone (Decadron)]] 4 mg PO twice to day on days -1 to 2
-*In Sequist et al. 2013: Patients "received folic acid, vitamin B12, and dexamethasone, as per package recommendations for [[Pemetrexed (Alimta)]]."
+'''21-day cycle for 6 cycles'''
+</div></div>
-'''21-day cycle for 4 to 6 cycles'''
 ===References===
-# '''JMDB:''' Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. Epub 2008 May 27. [https://doi.org/10.1200/jco.2007.15.0375 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/18506025 PubMed]
+# '''JMDB:''' Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. Epub 2008 May 27. [https://doi.org/10.1200/jco.2007.15.0375 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18506025/ PubMed]
 ==Cisplatin & Vinblastine {{#subobject:2fe6d3|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 VP: '''<u>V</u>'''inblastine & '''<u>P</u>'''latinol (Cisplatin)
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:c5e07c|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 436: / Line 542: @@
 |[https://doi.org/10.1200/JCO.1994.12.6.1113 Kosty et al. 1994 (CALGB 8931)]
 |1989-1991
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|VP & Hydrazine
+|[[#Cisplatin.2C_Hydrazine.2C_Vinblastine_999|VP & Hydrazine]]
-|style="background-color:#ffffbf"|Seems not superior
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]]
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
-*[[Vinblastine (Velban)]]
+*[[Vinblastine (Velban)]] as follows:
+**Cycle 1: 5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+**Cycle 2 onwards: 5 mg/m<sup>2</sup> IV once per day on days 1 & 15
+'''28-day cycles'''
+</div></div>
 ===References===
-# '''CALGB 8931:''' Kosty MP, Fleishman SB, Herndon JE 2nd, Coughlin K, Kornblith AB, Scalzo A, Morris JC, Mortimer J, Green MR; [[Study_Groups#CALGB|CALGB]]. Cisplatin, vinblastine, and hydrazine sulfate in advanced, non-small-cell lung cancer: a randomized placebo-controlled, double-blind phase III study of the Cancer and Leukemia Group B. J Clin Oncol. 1994 Jun;12(6):1113-20. [https://doi.org/10.1200/JCO.1994.12.6.1113 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8201372 PubMed]
+# '''CALGB 8931:''' Kosty MP, Fleishman SB, Herndon JE 2nd, Coughlin K, Kornblith AB, Scalzo A, Morris JC, Mortimer J, Green MR; [[Study_Groups#CALGB|CALGB]]. Cisplatin, vinblastine, and hydrazine sulfate in advanced, non-small-cell lung cancer: a randomized placebo-controlled, double-blind phase III study of the Cancer and Leukemia Group B. J Clin Oncol. 1994 Jun;12(6):1113-20. [https://doi.org/10.1200/JCO.1994.12.6.1113 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8201372/ PubMed]
 ==Cisplatin & Vindesine {{#subobject:80fe2|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 VP: '''<u>V</u>'''indesine & '''<u>P</u>'''latinol (Cisplatin)
 <br>VdsC: '''<u>V</u>'''in'''<u>d</u>'''e'''<u>s</u>'''ine & '''<u>C</u>'''isplatin
-===Regimen {{#subobject:2d16cd|Variant=1}}===
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #1, 80/3 {{#subobject:2d16cd|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.1986.4.1.14 Ruckdeschel et al. 1986 (ECOG E1581)]
+|[https://doi.org/10.1111/j.1440-1843.1996.tb00010.x Masutani et al. 1999]
-|1981-1983
+|1987-1992
-|style="background-color:#1a9851"|Phase III (E-de-esc)
+|style="background-color:#1a9851"|Phase 3 (C)
-|1. [[Non-small_cell_lung_cancer_-_historical#CAMP|CAMP]]<br> 2. [[Non-small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29|EC]]<br> 3. [[#MVP_.28Vinblastine.29|MVP]]
+|1. [[Stub#PVI|PVI]]<br>2. [[#MVP_.28Vindesine.29|PVM]]
-|style="background-color:#ffffbf"|Seems not superior
+|style="background-color:#ffffbf"|Did not meet endpoint of OS
+|-
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747545/ Negoro et al. 2003]
+|rowspan=2|1995-1998
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
+|1. [[Non-small_cell_lung_cancer#Cisplatin_.26_Irinotecan_.28IC.29|Cisplatin & Irinotecan]]
+| style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+|-
+|2. [[#Irinotecan_monotherapy_888|Irinotecan]]
+| style="background-color:#d3d3d3" |Not reported
 |-
-|[https://doi.org/10.1200/JCO.1988.6.4.633 Rapp et al. 1988]
+|[https://doi.org/10.1200/JCO.2004.06.114 Kubota et al. 2004]
-|1983-1986
+|1998-2000
-|style="background-color:#1a9851"|Phase III (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
-|[[#Best_supportive_care|Best supportive care]]
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_.28DC.29_3|Cisplatin & Docetaxel]]
-| style="background-color:#1a9850" |Superior OS
+| style="background-color:#fc8d59" |Seems to have inferior OS (primary endpoint)
 |-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1440-1843.1996.tb00010.x Masutani et al. 1999]
+|}
-|1987-1992
+<div class="toccolours" style="background-color:#b3e2cd">
-|style="background-color:#1a9851"|Phase III (C)
+====Chemotherapy====
-|1. [[Stub#PVI|PVI]]<br> 2. [[#MVP_.28Vindesine.29|PVM]]
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 1 to 2 hours once on day 1
-|style="background-color:#ffffbf"|Seems not superior
+*[[Vindesine (Eldisine)]] 3 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15
+'''28-day cycle for 2 or more cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #2, 100/3; split-dose cisplatin {{#subobject:2d1spd|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.lungcancerjournal.info/article/S0169-5002(02)00008-9/fulltext Kodani et al. 2002]
+|[https://doi.org/10.1016/s0169-5002(02)00008-9 Kodani et al. 2002]
 |1987-1992
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[Stub#PVI|PVI]]
-|style="background-color:#ffffbf"|Seems not superior
+|style="background-color:#ffffbf"|Did not meet endpoint of ORR
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747545/ Negoro et al. 2003]
+|}
-|1995-1998
+<div class="toccolours" style="background-color:#b3e2cd">
-|style="background-color:#1a9851"|Phase III (C)
+====Chemotherapy====
-|[[Non-small_cell_lung_cancer#Cisplatin_.26_Irinotecan_.28IC.29|Cisplatin & Irinotecan]]
+*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
-|style="background-color:#ffffbf"|Seems not superior
+*[[Vindesine (Eldisine)]] 3 mg/m<sup>2</sup> IV once per day on days 1 & 8
+'''28-day cycle for 5 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #3, 100/3; capped vindesine {{#subobject:2d100d|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://doi.org/10.1023/a:1012208711013 Vansteenkiste et al. 2001]
 |1996-1999
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[#Gemcitabine_monotherapy|Gemcitabine]]
 | style="background-color:#fc8d59" |Seems to have inferior clinical benefit
 |-
-|[https://doi.org/10.1200/JCO.2004.06.114 Kubota et al. 2004]
+|}
-|1998-2000
+<div class="toccolours" style="background-color:#b3e2cd">
-|style="background-color:#1a9851"|Phase III (E-switch-ic)
+====Chemotherapy====
-|[[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_.28DC.29_3|Cisplatin & Docetaxel]]
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 1 to 4 hours once on day 1
+*[[Vindesine (Eldisine)]] 3 mg/m<sup>2</sup> (maximum dose of 5 mg) IV once per day on days 1 & 15
+'''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #4, 120/3, 4-week induction {{#subobject:2d420d|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1988.6.4.633 Rapp et al. 1988]
+|1983-1986
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[#Best_supportive_care|Best supportive care]]
+| style="background-color:#1a9850" |Superior OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] as follows:
+**Cycle 1: 120 mg/m<sup>2</sup> IV once per day on days 1 & 29
+**Cycle 2 onwards: 120 mg/m<sup>2</sup> IV once on day 1
+*[[Vindesine (Eldisine)]] as follows:
+**Cycle 1: 3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 36, 50
+**Cycle 2 onwards: 3 mg/m<sup>2</sup> IV once per day on days 1, 15, 29
+'''9-week course, then 42-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #5, 120/3, 5-week induction {{#subobject:2d425d|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1986.4.1.14 Ruckdeschel et al. 1986 (ECOG E1581)]
+|1981-1983
+|style="background-color:#1a9851"|Phase 3 (E-de-esc)
+|1. [[#CAMP|CAMP]]<br>2. [[Non-small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29|EC]]<br> 3. [[#MVP_.28Vinblastine.29|MVP]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] as follows:
+**Cycle 1: 120 mg/m<sup>2</sup> IV once per day on days 1 & 29
+**Cycle 2 onwards: 120 mg/m<sup>2</sup> IV once on day 1
+*[[Vindesine (Eldisine)]] as follows:
+**Cycle 1: 3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 43, 57
+**Cycle 2 onwards: 3 mg/m<sup>2</sup> IV once per day on days 8, 22, 36
+'''10-week course, then 42-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #6, 120/3, 6-week induction {{#subobject:2d120d|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+| rowspan="2" |[https://doi.org/10.1200/JCO.1994.12.2.360 Le Chevalier et al. 1994]
+| rowspan="2" |1989-1991
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
+|1. [[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine_.28CVb.29_3|CVb]]
 | style="background-color:#fc8d59" |Seems to have inferior OS
+|-
+|2. [[Non-small_cell_lung_cancer_-_historical#Vinorelbine_monotherapy|Vinorelbine]]
+| style="background-color:#d3d3d3" |Not reported
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]]
+*[[Cisplatin (Platinol)]] as follows:
-*[[Vindesine (Eldisine)]]
+**Cycle 1: 120 mg/m<sup>2</sup> IV once per day on days 1 & 29
+**Cycle 2 onwards: 120 mg/m<sup>2</sup> IV once on day 29
+*[[Vindesine (Eldisine)]] as follows:
+**Cycle 1: 3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36
+**Cycle 2 onwards: 3 mg/m<sup>2</sup> IV once per day on days 1, 15, 29
+'''42-day cycles'''
+</div></div>
 ===References===
-# '''ECOG E1581:''' Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. [https://doi.org/10.1200/JCO.1986.4.1.14 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3510278 PubMed]
+# '''ECOG E1581:''' Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. [https://doi.org/10.1200/JCO.1986.4.1.14 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/3510278/ PubMed]
-# Rapp E, Pater JL, Willan A, Cormier Y, Murray N, Evans WK, Hodson DI, Clark DA, Feld R, Arnold AM, Ayoub JI, Wilson KS, Latreille J, Wierzbicki RF, Hill DP. Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial. J Clin Oncol. 1988 Apr;6(4):633-41. [https://doi.org/10.1200/JCO.1988.6.4.633 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2833577 PubMed]
+# Rapp E, Pater JL, Willan A, Cormier Y, Murray N, Evans WK, Hodson DI, Clark DA, Feld R, Arnold AM, Ayoub JI, Wilson KS, Latreille J, Wierzbicki RF, Hill DP. Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial. J Clin Oncol. 1988 Apr;6(4):633-41. [https://doi.org/10.1200/JCO.1988.6.4.633 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2833577/ PubMed]
-# Masutani M, Akusawa H, Kadota A, Ohchi Y, Takahashi N, Tanigawa S, Koya Y, Horie T. A phase III randomized trial of cisplatin plus vindesine versus cisplatin plus vindesine plus mitomycin C versus cisplatin plus vindesine plus ifosfamide for advanced non-small-cell lung cancer. Respirology. 1996 Mar;1(1):49-54. [https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1440-1843.1996.tb00010.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/9432405 PubMed]
+#Le Chevalier T, Brisgand D, Douillard JY, Pujol JL, Alberola V, Monnier A, Riviere A, Lianes P, Chomy P, Cigolari S, Gottfried M, Ruffle P, Panizo A, Gaspard MH, Ravaioli A, Besenval M, Besson F, Martinez A, Berthaud P, Tursz T. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients. J Clin Oncol. 1994 Feb;12(2):360-7. [https://doi.org/10.1200/JCO.1994.12.2.360 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8113844/ PubMed]
-# Vansteenkiste JF, Vandebroek JE, Nackaerts KL, Weynants P, Valcke YJ, Verresen DA, Devogelaere RC, Marien SA, Humblet YP, Dams NL; Leuven Lung Cancer Group. Clinical-benefit response in advanced non-small-cell lung cancer: a multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine. Ann Oncol. 2001 Sep;12(9):1221-30. [https://doi.org/10.1023/a:1012208711013 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11697832 PubMed]
+# Masutani M, Akusawa H, Kadota A, Ohchi Y, Takahashi N, Tanigawa S, Koya Y, Horie T. A phase III randomized trial of cisplatin plus vindesine versus cisplatin plus vindesine plus mitomycin C versus cisplatin plus vindesine plus ifosfamide for advanced non-small-cell lung cancer. Respirology. 1996 Mar;1(1):49-54. [https://doi.org/10.1111/j.1440-1843.1996.tb00010.x link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9432405/ PubMed]
-# Kodani T, Ueoka H, Kiura K, Tabata M, Takigawa N, Segawa Y, Moritaka T, Hiraki S, Harada M, Tanimoto M. A phase III randomized trial comparing vindesine and cisplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer: long-term follow-up results and analysis of prognostic factors. Lung Cancer. 2002 Jun;36(3):313-9. [https://www.lungcancerjournal.info/article/S0169-5002(02)00008-9/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/12009244 PubMed]
+# Vansteenkiste JF, Vandebroek JE, Nackaerts KL, Weynants P, Valcke YJ, Verresen DA, Devogelaere RC, Marien SA, Humblet YP, Dams NL; Leuven Lung Cancer Group. Clinical-benefit response in advanced non-small-cell lung cancer: a multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine. Ann Oncol. 2001 Sep;12(9):1221-30. [https://doi.org/10.1023/a:1012208711013 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11697832/ PubMed]
-# Negoro S, Masuda N, Takada Y, Sugiura T, Kudoh S, Katakami N, Ariyoshi Y, Ohashi Y, Niitani H, Fukuoka M; CPT-11 Lung Cancer Study Group West. Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer. Br J Cancer. 2003 Feb 10;88(3):335-41. [https://www.nature.com/articles/6600725 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747545/ link to PMC article] '''contains verified protocol'''  [https://pubmed.ncbi.nlm.nih.gov/12569373 PubMed]
+# Kodani T, Ueoka H, Kiura K, Tabata M, Takigawa N, Segawa Y, Moritaka T, Hiraki S, Harada M, Tanimoto M. A phase III randomized trial comparing vindesine and cisplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer: long-term follow-up results and analysis of prognostic factors. Lung Cancer. 2002 Jun;36(3):313-9. [https://doi.org/10.1016/s0169-5002(02)00008-9 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12009244/ PubMed]
-# Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, Sugiura T, Kawahara M, Yokoyama A, Yokota S, Yoneda S, Matsui K, Kudo S, Shibuya M, Isobe T, Segawa Y, Nishiwaki Y, Ohashi Y, Niitani H; Japanese Taxotere Lung Cancer Study Group. Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: the Japanese Taxotere Lung Cancer Study Group. J Clin Oncol. 2004 Jan 15;22(2):254-61. [https://doi.org/10.1200/JCO.2004.06.114 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14722033 PubMed]
+# Negoro S, Masuda N, Takada Y, Sugiura T, Kudoh S, Katakami N, Ariyoshi Y, Ohashi Y, Niitani H, Fukuoka M; CPT-11 Lung Cancer Study Group West. Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer. Br J Cancer. 2003 Feb 10;88(3):335-41. [https://doi.org/10.1038/sj.bjc.6600725 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747545/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors'''  [https://pubmed.ncbi.nlm.nih.gov/12569373/ PubMed]
+# Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, Sugiura T, Kawahara M, Yokoyama A, Yokota S, Yoneda S, Matsui K, Kudo S, Shibuya M, Isobe T, Segawa Y, Nishiwaki Y, Ohashi Y, Niitani H; Japanese Taxotere Lung Cancer Study Group. Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: the Japanese Taxotere Lung Cancer Study Group. J Clin Oncol. 2004 Jan 15;22(2):254-61. [https://doi.org/10.1200/JCO.2004.06.114 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/14722033/ PubMed]
 ==Docetaxel monotherapy {{#subobject:ec36b5|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#ee6b6e">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:dd8369|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.lungcancerjournal.info/article/S0169-5002(00)00094-5/fulltext Roszkowski et al. 2000]
+|[https://doi.org/10.1016/s0169-5002(00)00094-5 Roszkowski et al. 2000]
-|1995-NR
+|1995 to not reported
-|style="background-color:#1a9851"|Phase III (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-esc)
 |[[#Best_supportive_care|Best supportive care]]
 | style="background-color:#91cf60" |Seems to have superior OS
 |-
-|[https://www.lungcancerjournal.info/article/S0169-5002(07)00427-8/fulltext Georgoulias et al. 2007]
+|[https://doi.org/10.1016/j.lungcan.2007.07.021 Georgoulias et al. 2007]
 |2002-2004
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[#Docetaxel_.26_Gemcitabine|DG]]
 | style="background-color:#fc8d59" |Seems to have inferior OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]]
+*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+'''21-day cycles'''
+</div></div>
 ===References===
-# Roszkowski K, Pluzanska A, Krzakowski M, Smith AP, Saigi E, Aasebo U, Parisi A, Pham Tran N, Olivares R, Berille J. A multicenter, randomized, phase III study of docetaxel plus best supportive care versus best supportive care in chemotherapy-naive patients with metastatic or non-resectable localized non-small cell lung cancer (NSCLC). Lung Cancer. 2000 Mar;27(3):145-57. [https://www.lungcancerjournal.info/article/S0169-5002(00)00094-5/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/10699688 PubMed]
+# Roszkowski K, Pluzanska A, Krzakowski M, Smith AP, Saigi E, Aasebo U, Parisi A, Pham Tran N, Olivares R, Berille J. A multicenter, randomized, phase III study of docetaxel plus best supportive care versus best supportive care in chemotherapy-naive patients with metastatic or non-resectable localized non-small cell lung cancer (NSCLC). Lung Cancer. 2000 Mar;27(3):145-57. [https://doi.org/10.1016/s0169-5002(00)00094-5 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10699688/ PubMed]
-# Georgoulias V, Androulakis N, Kotsakis A, Hatzidaki D, Syrigos K, Polyzos A, Agelidou A, Varthalitis I, Ziras N, Agelidou M, Chandrinos V, Boukovinas I, Geroyianni A, Vamvakas L, Mavroudis D. Docetaxel versus docetaxel plus gemcitabine as front-line treatment of patients with advanced non-small cell lung cancer: a randomized, multicenter phase III trial. Lung Cancer. 2008 Jan;59(1):57-63. Epub 2007 Aug 31. [https://www.lungcancerjournal.info/article/S0169-5002(07)00427-8/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/17765354 PubMed]
+# Georgoulias V, Androulakis N, Kotsakis A, Hatzidaki D, Syrigos K, Polyzos A, Agelidou A, Varthalitis I, Ziras N, Agelidou M, Chandrinos V, Boukovinas I, Geroyianni A, Vamvakas L, Mavroudis D. Docetaxel versus docetaxel plus gemcitabine as front-line treatment of patients with advanced non-small cell lung cancer: a randomized, multicenter phase III trial. Lung Cancer. 2008 Jan;59(1):57-63. Epub 2007 Aug 31. [https://doi.org/10.1016/j.lungcan.2007.07.021 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17765354/ PubMed]
 ==Docetaxel & Gemcitabine {{#subobject:80fe2|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 DG: '''<u>D</u>'''ocetaxel & '''<u>G</u>'''emcitabine
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:2d16cd|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.lungcancerjournal.info/article/S0169-5002(07)00427-8/fulltext Georgoulias et al. 2007]
+|[https://doi.org/10.1016/j.lungcan.2007.07.021 Georgoulias et al. 2007]
 |2002-2004
-|style="background-color:#1a9851"|Phase III (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-esc)
 |[[#Docetaxel_monotherapy|Docetaxel]]
-| style="background-color:#91cf60" |Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS (primary endpoint)<br>Median OS: 9.4 vs 8.3 mo
 |-
 |}
-''Note: while this is a superior arm of a phase III RCT, the comparator (single-agent docetaxel) is not usually used in the first-line treatment and this regimen is not currently recommended by ESMO guidelines.''
+''Note: while this was the superior arm of a phase 3 RCT, the comparator (single-agent docetaxel) is not usually used in the first-line treatment and this regimen is not currently recommended by ESMO guidelines.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]]
+*[[Docetaxel (Taxotere)]] 1100 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Gemcitabine (Gemzar)]]
+*[[Gemcitabine (Gemzar)]] 75 mg/m<sup>2</sup> IV once on day 8
+'''21-day cycles'''
+</div></div>
+===References===
+# Georgoulias V, Androulakis N, Kotsakis A, Hatzidaki D, Syrigos K, Polyzos A, Agelidou A, Varthalitis I, Ziras N, Agelidou M, Chandrinos V, Boukovinas I, Geroyianni A, Vamvakas L, Mavroudis D. Docetaxel versus docetaxel plus gemcitabine as front-line treatment of patients with advanced non-small cell lung cancer: a randomized, multicenter phase III trial. Lung Cancer. 2008 Jan;59(1):57-63. Epub 2007 Aug 31. [https://doi.org/10.1016/j.lungcan.2007.07.021 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17765354/ PubMed]
+==FULV {{#subobject:a93a|Regimen=1}}==
+FULV: 5-'''<u>FU</u>''' & '''<u>L</u>'''euco'''<u>V</u>'''orin
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen {{#subobject:2hc22c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1996.14.10.2774 Crawford et al. 1996]
+|1990-1992
+|style="background-color:#1a9851"|Randomized (C)
+|[[#Vinorelbine_monotherapy|Vinorelbine]]
+| style="background-color:#fc8d59" |Seems to have inferior OS
+|-
+|}
+''Note: To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given second'''
+*[[Leucovorin (Folinic acid)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given first'''
+'''28-day cycles'''
+</div></div>
 ===References===
-# Georgoulias V, Androulakis N, Kotsakis A, Hatzidaki D, Syrigos K, Polyzos A, Agelidou A, Varthalitis I, Ziras N, Agelidou M, Chandrinos V, Boukovinas I, Geroyianni A, Vamvakas L, Mavroudis D. Docetaxel versus docetaxel plus gemcitabine as front-line treatment of patients with advanced non-small cell lung cancer: a randomized, multicenter phase III trial. Lung Cancer. 2008 Jan;59(1):57-63. Epub 2007 Aug 31. [https://www.lungcancerjournal.info/article/S0169-5002(07)00427-8/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/17765354 PubMed]
+# Crawford J, O'Rourke M, Schiller JH, Spiridonidis CH, Yanovich S, Ozer H, Langleben A, Hutchins L, Koletsky A, Clamon G, Burman S, White R, Hohneker J. Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer. J Clin Oncol. 1996 Oct;14(10):2774-84. Erratum in: J Clin Oncol 1996 Dec;14(12):3175. Spiridonitis CH [corrected to Spiridonidis CH]. [https://doi.org/10.1200/JCO.1996.14.10.2774 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8874339/ PubMed]
 ==Ifosfamide & Gemcitabine {{#subobject:80fe2|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+IG: '''<u>I</u>'''fosfamide & '''<u>G</u>'''emcitabine
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #1, 3000/1000 {{#subobject:23occd|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://ar.iiarjournals.org/content/33/12/5477.long Berghmans et al. 2013 (ELCWP-01041)]
+|2003-2009
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#GIP|GIP]]<br>2. [[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_.28DC.29_3|DP]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[[#top|back to top]]
 |}
-IG: '''<u>I</u>'''fosfamide & '''<u>G</u>'''emcitabine
+''Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. Cycle length was not explicitly declared in the manuscript and was inferred from other variants.''
-===Regimen {{#subobject:2d16cd|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV once on day 1
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on day 1, 8, 15
+'''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #2, 4500/1000 {{#subobject:2d16cd|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 597: / Line 857: @@
 |[https://doi.org/10.1093/annonc/mdf154 Sculier et al. 2002]
 |1998-2000
-|style="background-color:#1a9851"|Phase III (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-esc)
-|1. [[#CCI|CCI]]<br> 2. [[Stub#CCG|CCG]]
+|1. [[#CCI|CCI]]<br>2. [[Stub#CCG|CCG]]
-| style="background-color:#ffffbf" |Seems not superior
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|[http://ar.iiarjournals.org/content/33/12/5477.long Berghmans et al. 2013 (ELCWP-01041)]
-|2003-2009
-|style="background-color:#1a9851"|Phase III (C)
-|1. [[#GIP|GIP]]<br> 2. [[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_.28DC.29_3|DP]]
-| style="background-color:#ffffbf" |Seems not superior
 |-
 |}
-''Note: this is an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator.''
+''Note: This was an experimental arm that did not meet its primary endpoint; included here because it was likely used to establish this regimen as a standard comparator.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Ifosfamide (Ifex)]]
+*[[Ifosfamide (Ifex)]] 4500 mg/m<sup>2</sup> IV once on day 1
-*[[Gemcitabine (Gemzar)]]
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on day 1, 8, 15
+'''28-day cycles'''
+</div></div>
 ===References===
-# Sculier JP, Lafitte JJ, Lecomte J, Berghmans T, Thiriaux J, Florin MC, Efremidis A, Alexopoulos CG, Recloux P, Ninane V, Mommen P, Paesmans M, Klastersky J; European Lung Cancer Working Party. A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer. Ann Oncol. 2002 Jun;13(6):874-82. [https://doi.org/10.1093/annonc/mdf154 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12123332 PubMed]
+# Sculier JP, Lafitte JJ, Lecomte J, Berghmans T, Thiriaux J, Florin MC, Efremidis A, Alexopoulos CG, Recloux P, Ninane V, Mommen P, Paesmans M, Klastersky J; European Lung Cancer Working Party. A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer. Ann Oncol. 2002 Jun;13(6):874-82. [https://doi.org/10.1093/annonc/mdf154 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12123332/ PubMed]
-# '''ELCWP-01041:''' Berghmans T, Lafitte JJ, Scherpereel A, Paesmans M, Lecomte J, Marco VG, Meert AP, Leclercq N, Sculier JP; European Lung Cancer Working Party. An ELCWP phase III trial comparing ifosfamide and cisplatin regimens in advanced NSCLC. Anticancer Res. 2013 Dec;33(12):5477-82. [http://ar.iiarjournals.org/content/33/12/5477.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/24324084 PubMed] NCT00622349
+# '''ELCWP-01041:''' Berghmans T, Lafitte JJ, Scherpereel A, Paesmans M, Lecomte J, Marco VG, Meert AP, Leclercq N, Sculier JP; European Lung Cancer Working Party. An ELCWP phase III trial comparing ifosfamide and cisplatin regimens in advanced NSCLC. Anticancer Res. 2013 Dec;33(12):5477-82. [https://ar.iiarjournals.org/content/33/12/5477.long link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24324084/ PubMed] [https://clinicaltrials.gov/study/NCT00622349 NCT00622349]
 ==Gemcitabine monotherapy {{#subobject:826de2|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#ee6b6e">
-|-
+===Regimen variant #1, 1000 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:4b26cd|Variant=1}}===
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:4b26cd|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 632: / Line 885: @@
 |[https://doi.org/10.1023/a:1012208711013 Vansteenkiste et al. 2001]
 |1996-1999
-|style="background-color:#1a9851"|Phase III (E-de-esc)
+|style="background-color:#1a9851"|Phase 3 (E-de-esc)
 |[[#Cisplatin_.26_Vindesine|Cisplatin & Vindesine]]
 | style="background-color:#91cf60" |Seems to have superior clinical benefit
+|-
+|}
+''Note: this regimen is considered current in elderly patients or those with poor PS; these trials were unselected by these parameters.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+'''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #2, 1250 mg/m<sup>2</sup>, 2 out of 3 weeks {{#subobject:4bincd|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://doi.org/10.1200/jco.2005.01.2781 Sederholm et al. 2005]
 |1998-2001
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (E-de-esc)
 |[[Non-small_cell_lung_cancer#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]]
 | style="background-color:#fc8d59" |Seems to have inferior OS
@@ Line 644: / Line 913: @@
 |}
 ''Note: this regimen is considered current in elderly patients or those with poor PS; these trials were unselected by these parameters.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Gemcitabine (Gemzar)]]
+*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
+'''21-day cycles'''
+</div></div>
 ===References===
-# Vansteenkiste JF, Vandebroek JE, Nackaerts KL, Weynants P, Valcke YJ, Verresen DA, Devogelaere RC, Marien SA, Humblet YP, Dams NL; Leuven Lung Cancer Group. Clinical-benefit response in advanced non-small-cell lung cancer: a multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine. Ann Oncol. 2001 Sep;12(9):1221-30. [https://doi.org/10.1023/a:1012208711013 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11697832 PubMed]
+# Vansteenkiste JF, Vandebroek JE, Nackaerts KL, Weynants P, Valcke YJ, Verresen DA, Devogelaere RC, Marien SA, Humblet YP, Dams NL; Leuven Lung Cancer Group. Clinical-benefit response in advanced non-small-cell lung cancer: a multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine. Ann Oncol. 2001 Sep;12(9):1221-30. [https://doi.org/10.1023/a:1012208711013 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11697832/ PubMed]
-# Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, Gawande SR. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: Swedish Lung Cancer Study Group. J Clin Oncol. 2005 Nov 20;23(33):8380-8. [https://doi.org/10.1200/jco.2005.01.2781 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16293868 PubMed]
+# Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, Gawande SR. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol. 2005 Nov 20;23(33):8380-8. [https://doi.org/10.1200/jco.2005.01.2781 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16293868/ PubMed]
 ==GIP {{#subobject:2c098d|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 GIP: '''<u>G</u>'''emcitabine, '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:9a4cf6|Variant=1}}===
 {| class="wikitable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://doi.org/10.1093/annonc/mdm084 Sculier et al. 2007]
 |2000-2004
-| style="background-color:#91cf61" |Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Gemcitabine (Gemzar)]]
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Ifosfamide (Ifex)]]
+*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV once on day 1
-*[[Cisplatin (Platinol)]]
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 3 cycles'''
+</div></div>
 ===References===
-# Sculier JP, Lafitte JJ, Lecomte J, Alexopoulos CG, Van Cutsem O, Giner V, Efremidis A, Berchier MC, Collon T, Meert AP, Scherpereel A, Ninane V, Paesmans M, Berghmans T; European Lung Cancer Working Party. A phase III randomised trial comparing sequential chemotherapy using cisplatin-based regimen and paclitaxel to cisplatin-based chemotherapy alone in advanced non-small-cell lung cancer. Ann Oncol. 2007 Jun;18(6):1037-42. Epub 2007 Apr 2. [https://doi.org/10.1093/annonc/mdm084 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17404152 PubMed]
+# Sculier JP, Lafitte JJ, Lecomte J, Alexopoulos CG, Van Cutsem O, Giner V, Efremidis A, Berchier MC, Collon T, Meert AP, Scherpereel A, Ninane V, Paesmans M, Berghmans T; European Lung Cancer Working Party. A phase III randomised trial comparing sequential chemotherapy using cisplatin-based regimen and paclitaxel to cisplatin-based chemotherapy alone in advanced non-small-cell lung cancer. Ann Oncol. 2007 Jun;18(6):1037-42. Epub 2007 Apr 2. [https://doi.org/10.1093/annonc/mdm084 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17404152/ PubMed]
 ==MACC {{#subobject:3f2f0c|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 MACC: '''<u>M</u>'''ethotrexate, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>C</u>'''CNU (Lomustine)
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:cec9d6|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://jamanetwork.com/journals/jama/article-abstract/353407 Chahinian et al. 1977]
+|[https://doi.org/10.1001/jama.1977.03270490032019 Chahinian et al. 1977]
-|NR
+|Not reported
 | style="background-color:#91cf61" |Non-randomized
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
 |-
-|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19820901)50:5%3C845::AID-CNCR2820500507%3E3.0.CO;2-S/abstract Cormier et al. 1982]
+|[https://doi.org/10.1002/1097-0142(19820901)50:5%3C845::AID-CNCR2820500507%3E3.0.CO;2-S Cormier et al. 1982]
-|NR
+|Not reported
-|style="background-color:#1a9851"|Phase III (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-esc)
 |[[#Placebo|Placebo]]
 |style="background-color:#1a9850"|Superior OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Methotrexate (MTX)]]
+*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once on day 1
-*[[Doxorubicin (Adriamycin)]]
+*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
-*[[Cyclophosphamide (Cytoxan)]]
+*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once on day 1
-*[[Lomustine (CCNU)]]
+*[[Lomustine (CCNU)]] 30 mg/m<sup>2</sup> PO once on day 1, taken on an empty stomach
+'''21-day cycles'''
+</div></div>
 ===References===
-# Chahinian PA, Arnold DJ, Cohen JM, Purpora DP, Jaffrey IS, Teirstein AS, Kirschner PA, Holland JF. Chemotherapy for bronchogenic carcinoma: methotrexate, doxorubicin, cyclophosphamide, and lomustine. JAMA. 1977 May 30;237(22):2392-6. [https://jamanetwork.com/journals/jama/article-abstract/353407 link to original article] [https://pubmed.ncbi.nlm.nih.gov/576939 PubMed]
+# Chahinian PA, Arnold DJ, Cohen JM, Purpora DP, Jaffrey IS, Teirstein AS, Kirschner PA, Holland JF. Chemotherapy for bronchogenic carcinoma: methotrexate, doxorubicin, cyclophosphamide, and lomustine. JAMA. 1977 May 30;237(22):2392-6. [https://doi.org/10.1001/jama.1977.03270490032019 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/576939/ PubMed]
-# Cormier Y, Bergeron D, La Forge J, Lavandier M, Fournier M, Chenard J, Desmeules M. Benefits of polychemotherapy in advanced non-small-cell bronchogenic carcinoma. Cancer. 1982 Sep 1;50(5):845-9. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19820901)50:5%3C845::AID-CNCR2820500507%3E3.0.CO;2-S/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/7093924 PubMed]
+# Cormier Y, Bergeron D, La Forge J, Lavandier M, Fournier M, Chenard J, Desmeules M. Benefits of polychemotherapy in advanced non-small-cell bronchogenic carcinoma. Cancer. 1982 Sep 1;50(5):845-9. [https://doi.org/10.1002/1097-0142(19820901)50:5%3C845::AID-CNCR2820500507%3E3.0.CO;2-S link to original article] [https://pubmed.ncbi.nlm.nih.gov/7093924/ PubMed]
 ==MIC {{#subobject:d1b4dd|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+MIC: '''<u>M</u>'''itomycin, '''<u>I</u>'''fosfamide, '''<u>C</u>'''isplatin
+<br>MIP: '''<u>M</u>'''itomycin, '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #1 {{#subobject:9905c2|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1002/cncr.11535 Danson et al. 2003]
+|1997-2001
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[Non-small_cell_lung_cancer#Carboplatin_.26_Gemcitabine_.28GCb.29|GC]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 |-
-|[[#top|back to top]]
 |}
-MIC: '''<u>M</u>'''itomycin, '''<u>I</u>'''fosfamide, '''<u>C</u>'''isplatin
+<div class="toccolours" style="background-color:#b3e2cd">
-<br>MIP: '''<u>M</u>'''itomycin, '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
+====Chemotherapy====
-===Regimen {{#subobject:99a9f2|Variant=1}}===
+*[[Mitomycin (Mutamycin)]] 6 mg/m<sup>2</sup> IV bolus once on day 1
+*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 4 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #2 {{#subobject:99a9f2|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 729: / Line 1,019: @@
 |[https://doi.org/10.1200/JCO.1999.17.10.3188 Cullen et al. 1999 (MIC2)]
 |1988-1996
-|style="background-color:#1a9851"|Phase III (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-esc)
 |[[#Best_supportive_care|Best supportive care]]
 |style="background-color:#91cf60"|Seems to have superior OS
-|-
-|[https://doi.org/10.1200/JCO.1999.17.11.3522 Crinò et al. 1999]
-|1995-1997
-|style="background-color:#1a9851"|Phase III (C)
-|[[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
-| style="background-color:#fc8d59" |Seems to have inferior ORR
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363584/ Sculier et al. 2000]
 |1995-1998
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[Stub#CarboMIP|CarboMIP]]
-|style="background-color:#ffffbf"|Seems not superior
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
-|-
-|[https://onlinelibrary.wiley.com/doi/10.1002/cncr.11535/abstract Danson et al. 2003]
-|1997-2001
-|style="background-color:#1a9851"|Phase III (C)
-|[[Non-small_cell_lung_cancer#Carboplatin_.26_Gemcitabine_.28GCb.29|GC]]
-|style="background-color:#ffffbf"|Seems not superior
 |-
 |[https://doi.org/10.1093/annonc/mdl078 Booton et al. 2006 (BTOG1)]
-|2000-2001
+|2001-06 to 2002-11
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[Non-small_cell_lung_cancer#Carboplatin_.26_Docetaxel|DCb]]
-|style="background-color:#ffffbf"|Seems not superior
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Mitomycin (Mutamycin)]]
+*[[Mitomycin (Mutamycin)]] 6 mg/m<sup>2</sup> IV bolus once on day 1, '''given first'''
-*[[Ifosfamide (Ifex)]]
+*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given second'''
-*[[Cisplatin (Platinol)]]
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given third, 3 hours after end of ifosfamide'''
+====Supportive therapy====
+*[[Mesna (Mesnex)]] 1000 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given with ifosfamide''', then 500 mg/m<sup>2</sup> IV bolus at 4 hours and 8 hours after ifosfamide
+'''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #3, higher-dose cisplatin {{#subobject:99aci2|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1999.17.11.3522 Crinò et al. 1999]
+|1995-1997
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
+| style="background-color:#fc8d59" |Seems to have inferior ORR
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Mitomycin (Mutamycin)]] 6 mg/m<sup>2</sup> IV once on day 1
+*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 2
+====Supportive therapy====
+*[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup> IV once on day 1, '''given with ifosfamide''', then 600 mg/m<sup>2</sup> IV at 4 hours and 8 hours after ifosfamide
+'''28-day cycles'''
+</div></div>
 ===References===
-# '''MIC2:''' Cullen MH, Billingham LJ, Woodroffe CM, Chetiyawardana AD, Gower NH, Joshi R, Ferry DR, Rudd RM, Spiro SG, Cook JE, Trask C, Bessell E, Connolly CK, Tobias J, Souhami RL. Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life. J Clin Oncol. 1999 Oct;17(10):3188-94. [https://doi.org/10.1200/JCO.1999.17.10.3188 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10506617 PubMed]
+# '''MIC2:''' Cullen MH, Billingham LJ, Woodroffe CM, Chetiyawardana AD, Gower NH, Joshi R, Ferry DR, Rudd RM, Spiro SG, Cook JE, Trask C, Bessell E, Connolly CK, Tobias J, Souhami RL. Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life. J Clin Oncol. 1999 Oct;17(10):3188-94. [https://doi.org/10.1200/JCO.1999.17.10.3188 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10506617/ PubMed]
-# Crinò L, Scagliotti GV, Ricci S, De Marinis F, Rinaldi M, Gridelli C, Ceribelli A, Bianco R, Marangolo M, Di Costanzo F, Sassi M, Barni S, Ravaioli A, Adamo V, Portalone L, Cruciani G, Masotti A, Ferrara G, Gozzelino F, Tonato M. Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol. 1999 Nov;17(11):3522-30. [https://doi.org/10.1200/JCO.1999.17.11.3522 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/10550150 PubMed]
+# Crinò L, Scagliotti GV, Ricci S, De Marinis F, Rinaldi M, Gridelli C, Ceribelli A, Bianco R, Marangolo M, Di Costanzo F, Sassi M, Barni S, Ravaioli A, Adamo V, Portalone L, Cruciani G, Masotti A, Ferrara G, Gozzelino F, Tonato M. Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol. 1999 Nov;17(11):3522-30. [https://doi.org/10.1200/JCO.1999.17.11.3522 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10550150/ PubMed]
-# Sculier JP, Lafitte JJ, Paesmans M, Thiriaux J, Alexopoulos CG, Baumöhl J, Schmerber J, Koumakis G, Florin MC, Zacharias C, Berghmans T, Mommen P, Ninane V, Klastersky J. Phase III randomized trial comparing moderate-dose cisplatin to combined cisplatin and carboplatin in addition to mitomycin and ifosfamide in patients with stage IV non-small-cell lung cancer. Br J Cancer. 2000 Nov;83(9):1128-35. [https://www.nature.com/articles/6691413 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363584/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/11027424 PubMed]
+# Sculier JP, Lafitte JJ, Paesmans M, Thiriaux J, Alexopoulos CG, Baumöhl J, Schmerber J, Koumakis G, Florin MC, Zacharias C, Berghmans T, Mommen P, Ninane V, Klastersky J. Phase III randomized trial comparing moderate-dose cisplatin to combined cisplatin and carboplatin in addition to mitomycin and ifosfamide in patients with stage IV non-small-cell lung cancer. Br J Cancer. 2000 Nov;83(9):1128-35. [https://doi.org/10.1054/bjoc.2000.1413 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363584/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11027424/ PubMed]
-# Danson S, Middleton MR, O'Byrne KJ, Clemons M, Ranson M, Hassan J, Anderson H, Burt PA, Fairve-Finn C, Stout R, Dowd I, Ashcroft L, Beresford C, Thatcher N. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003 Aug 1;98(3):542-53. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.11535/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/12879472 PubMed]
+# Danson S, Middleton MR, O'Byrne KJ, Clemons M, Ranson M, Hassan J, Anderson H, Burt PA, Fairve-Finn C, Stout R, Dowd I, Ashcroft L, Beresford C, Thatcher N. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003 Aug 1;98(3):542-53. [https://doi.org/10.1002/cncr.11535 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12879472/ PubMed]
-# '''BTOG1:''' Booton R, Lorigan P, Anderson H, Baka S, Ashcroft L, Nicolson M, O'Brien M, Dunlop D, O'Byrne K, Laurence V, Snee M, Dark G, Thatcher N. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol. 2006 Jul;17(7):1111-9. Epub 2006 Apr 7. [https://doi.org/10.1093/annonc/mdl078 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16603599 PubMed]
+# '''BTOG1:''' Booton R, Lorigan P, Anderson H, Baka S, Ashcroft L, Nicolson M, O'Brien M, Dunlop D, O'Byrne K, Laurence V, Snee M, Dark G, Thatcher N. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol. 2006 Jul;17(7):1111-9. Epub 2006 Apr 7. [https://doi.org/10.1093/annonc/mdl078 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16603599/ PubMed]
 ==MVP (Vinblastine) {{#subobject:eb48eb|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+MVP: '''<u>M</u>'''itomycin, '''<u>V</u>'''inblastine, '''<u>P</u>'''latinol (Cisplatin)
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #1 {{#subobject:88mvp8|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1002/cncr.11535 Danson et al. 2003]
+|1997-2001
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[Non-small_cell_lung_cancer#Carboplatin_.26_Gemcitabine_.28GCb.29|GC]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 |-
-|[[#top|back to top]]
 |}
-MVP: '''<u>M</u>'''itomycin, '''<u>V</u>'''inblastine, '''<u>P</u>'''latinol (Cisplatin)
+<div class="toccolours" style="background-color:#b3e2cd">
-===Regimen {{#subobject:883648|Variant=1}}===
+====Chemotherapy====
+*[[Mitomycin (Mutamycin)]] as follows:
+**Cycles 1, 2, 4: 8 mg/m<sup>2</sup> IV bolus once on day 1
+*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> (maximum dose of 10 mg) IV bolus once on day 1
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 4 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #2 {{#subobject:883648|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 786: / Line 1,114: @@
 |[https://doi.org/10.1200/JCO.1986.4.1.14 Ruckdeschel et al. 1986 (ECOG E1581)]
 |1981-1983
-|style="background-color:#1a9851"|Phase III (E-de-esc)
+|style="background-color:#1a9851"|Phase 3 (E-de-esc)
-|1. [[Non-small_cell_lung_cancer_-_historical#CAMP|CAMP]]<br> 2. [[Non-small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29|EC]]<br> 3. [[#Cisplatin_.26_Vindesine|VC]]
+|1. [[#CAMP|CAMP]]<br>2. [[Non-small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29|EC]]<br> 3. [[#Cisplatin_.26_Vindesine|VC]]
-|style="background-color:#ffffbf"|Seems not superior
+|style="background-color:#ffffbf"|Did not meet primary endpoint
 |-
 |[https://doi.org/10.1200/JCO.1989.7.11.1602 Bonomi et al. 1989 (ECOG E1583)]
-|1984-1985
+|1984-01 to 1985-07
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|1. VP<br> 2. MVP/CAMP<br> 3. Carboplatin<br> 4. Iproplatin
+|1. [[#Cisplatin_.26_Vinblastine_333|VP]]<br>2. [[#MVP.2FCAMP_333|MVP/CAMP]]<br> 3. [[#Carboplatin_monotherapy_333|Carboplatin]]<br> 4. [[#Iproplatin_monotherapy_777|Iproplatin]]
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#fee08b" |Might have inferior OS
 |-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19921101)70:9%3C2281::AID-CNCR2820700912%3E3.0.CO;2-9 Veeder et al. 1992]
+|[https://doi.org/10.1002/1097-0142(19921101)70:9%3C2281::AID-CNCR2820700912%3E3.0.CO;2-9 Veeder et al. 1992]
-|NR
+|Not reported
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|Mitomycin
+|[[#Mitomycin_monotherapy_999|Mitomycin]]
 | style="background-color:#d9ef8b" |Might have superior OS
 |-
 |[https://doi.org/10.1200/JCO.2001.19.5.1336 Smith et al. 2001]
 |1995-1998
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[#MVP_.28Vinblastine.29|MVP]] x 3
-|style="background-color:#ffffbf"|Seems not superior
+|style="background-color:#ffffbf"|Did not meet co-primary endpoint of OS
-|-
-|[https://onlinelibrary.wiley.com/doi/10.1002/cncr.11535/abstract Danson et al. 2003]
-|1997-2001
-|style="background-color:#1a9851"|Phase III (C)
-|[[Non-small_cell_lung_cancer#Carboplatin_.26_Gemcitabine_.28GCb.29|GC]]
-|style="background-color:#ffffbf"|Seems not superior
 |-
 |[https://doi.org/10.1093/annonc/mdl078 Booton et al. 2006 (BTOG1)]
-|2001-2002
+|2001-06 to 2002-11
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[Non-small_cell_lung_cancer#Carboplatin_.26_Docetaxel|DCb]]
-|style="background-color:#ffffbf"|Seems not superior
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Mitomycin (Mutamycin)]]
+*[[Mitomycin (Mutamycin)]] 10 mg/m<sup>2</sup> IV over 5 to 15 minutes once on day 1
-*[[Vinblastine (Velban)]]
+*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV push once on day 1
-*[[Cisplatin (Platinol)]]
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 2 hours once on day 1
+'''28-day cycles'''
+</div></div>
 ===References===
-# '''ECOG E1581:''' Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. [https://doi.org/10.1200/JCO.1986.4.1.14 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3510278 PubMed]
+# '''ECOG E1581:''' Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. [https://doi.org/10.1200/JCO.1986.4.1.14 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3510278/ PubMed]
-# '''ECOG E1583:''' Bonomi PD, Finkelstein DM, Ruckdeschel JC, Blum RH, Green MD, Mason B, Hahn R, Tormey DC, Harris J, Comis R, Glick J. Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small-cell lung cancer: a study of the Eastern Cooperative Oncology Group. J Clin Oncol. 1989 Nov;7(11):1602-13. [https://doi.org/10.1200/JCO.1989.7.11.1602 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2553879 PubMed]
+# '''ECOG E1583:''' Bonomi PD, Finkelstein DM, Ruckdeschel JC, Blum RH, Green MD, Mason B, Hahn R, Tormey DC, Harris J, Comis R, Glick J. Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small-cell lung cancer: a study of the Eastern Cooperative Oncology Group. J Clin Oncol. 1989 Nov;7(11):1602-13. [https://doi.org/10.1200/JCO.1989.7.11.1602 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2553879/ PubMed]
-# Veeder MH, Jett JR, Su JQ, Mailliard JA, Foley JF, Dalton RJ, Etzell PS, Marschke RF Jr, Kardinal CG, Maksymiuk AW, Ebbert LP, Tazelaar HD, Witrak GA. A phase III trial of mitomycin C alone versus mitomycin C, vinblastine, and cisplatin for metastatic squamous cell lung carcinoma. Cancer. 1992 Nov 1;70(9):2281-7. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19921101)70:9%3C2281::AID-CNCR2820700912%3E3.0.CO;2-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1394057 PubMed]
+# Veeder MH, Jett JR, Su JQ, Mailliard JA, Foley JF, Dalton RJ, Etzell PS, Marschke RF Jr, Kardinal CG, Maksymiuk AW, Ebbert LP, Tazelaar HD, Witrak GA. A phase III trial of mitomycin C alone versus mitomycin C, vinblastine, and cisplatin for metastatic squamous cell lung carcinoma. Cancer. 1992 Nov 1;70(9):2281-7. [https://doi.org/10.1002/1097-0142(19921101)70:9%3C2281::AID-CNCR2820700912%3E3.0.CO;2-9 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/1394057/ PubMed]
-# Smith IE, O'Brien ME, Talbot DC, Nicolson MC, Mansi JL, Hickish TF, Norton A, Ashley S. Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin. J Clin Oncol. 2001 Mar 1;19(5):1336-43. [https://doi.org/10.1200/JCO.2001.19.5.1336 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11230476 PubMed]
+# Smith IE, O'Brien ME, Talbot DC, Nicolson MC, Mansi JL, Hickish TF, Norton A, Ashley S. Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin. J Clin Oncol. 2001 Mar 1;19(5):1336-43. [https://doi.org/10.1200/JCO.2001.19.5.1336 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11230476/ PubMed]
-# Danson S, Middleton MR, O'Byrne KJ, Clemons M, Ranson M, Hassan J, Anderson H, Burt PA, Fairve-Finn C, Stout R, Dowd I, Ashcroft L, Beresford C, Thatcher N. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003 Aug 1;98(3):542-53. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.11535/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/12879472 PubMed]
+# Danson S, Middleton MR, O'Byrne KJ, Clemons M, Ranson M, Hassan J, Anderson H, Burt PA, Fairve-Finn C, Stout R, Dowd I, Ashcroft L, Beresford C, Thatcher N. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003 Aug 1;98(3):542-53. [https://doi.org/10.1002/cncr.11535 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12879472/ PubMed]
-# '''BTOG1:''' Booton R, Lorigan P, Anderson H, Baka S, Ashcroft L, Nicolson M, O'Brien M, Dunlop D, O'Byrne K, Laurence V, Snee M, Dark G, Thatcher N. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol. 2006 Jul;17(7):1111-9. Epub 2006 Apr 7. [https://doi.org/10.1093/annonc/mdl078 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16603599 PubMed]
+# '''BTOG1:''' Booton R, Lorigan P, Anderson H, Baka S, Ashcroft L, Nicolson M, O'Brien M, Dunlop D, O'Byrne K, Laurence V, Snee M, Dark G, Thatcher N. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol. 2006 Jul;17(7):1111-9. Epub 2006 Apr 7. [https://doi.org/10.1093/annonc/mdl078 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16603599/ PubMed]
 ==MVP (Vindesine) {{#subobject:5258ea|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 MVP: '''<u>M</u>'''itomycin, '''<u>V</u>'''indesine, '''<u>P</u>'''latinol (Cisplatin)
 <br>PVM: '''<u>P</u>'''latinol (Cisplatin), '''<u>V</u>'''indesine, '''<u>M</u>'''itomycin
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:ffec94|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 851: / Line 1,172: @@
 |[https://doi.org/10.1093/oxfordjournals.annonc.a058834 González Barón et al. 1994]
 |1989-1992
-|style="background-color:#1a9851"|Phase III (E-switch-ic)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
-|MIP
+|[[#MIC_3|MIP]]
-| style="background-color:#ffffbf" |Seems not superior
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
 |[https://doi.org/10.1093/oxfordjournals.annonc.a010761 Gridelli et al. 1996]
 |1990-1994
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[Stub#MEV|MEV]]
-| style="background-color:#ffffbf" |Seems not superior
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
-|[https://www.lungcancerjournal.info/article/S0169-5002(01)00239-2/fulltext Jelić et al. 2001]
+|[https://doi.org/10.1016/s0169-5002(01)00239-2 Jelić et al. 2001]
 |1990-1996
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[Stub#MVC|MVC]]
 | style="background-color:#d73027" |Inferior OS
 |-
-|[https://www.ejcancer.com/article/S0959-8049(98)00231-7/fulltext Boni et al. 1998]
+|[https://doi.org/10.1016/s0959-8049(98)00231-7 Boni et al. 1998]
 |1992-1996
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[#MVP_.28Vindesine.29|MVP]]; CI
-| style="background-color:#ffffbf" |Seems not superior
+| style="background-color:#ffffbf" |Did not meet endpoint of OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Mitomycin (Mutamycin)]]
+*[[Mitomycin (Mutamycin)]] as follows:
-*[[Vindesine (Eldisine)]]
+**Cycles 1, 2, 4, 6: 8 mg/m<sup>2</sup> IV bolus once on day 1
-*[[Cisplatin (Platinol)]]
+*[[Vindesine (Eldisine)]] as follows:
+**Cycle 1: 3 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22
+**Cycles 2 to 6: 3 mg/m<sup>2</sup> IV bolus once per day on days 1 & 15
+*[[Cisplatin (Platinol)]] 125 mg/m<sup>2</sup> IV once on day 1
+'''28-day cycle for up to 6 cycles'''
+</div></div>
 ===References===
-# González Barón M, Feliu J, Espinosa E, García Girón C, Blanco E, Garrido P, Colmenarejo A, Ordóñez A, Moyano A, de la Gándara I, Zamora P; ONCOPAZ Cooperative Group. Comparison of two chemotherapeutic regimens--mitomycin + vindesine + cisplatin (MVP) vs mitomycin + ifosfamide + cisplatin (MIP)--in advanced non-small-cell lung cancer. Ann Oncol. 1994 Apr;5(4):323-7. [https://doi.org/10.1093/oxfordjournals.annonc.a058834 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8075028 PubMed]
+# González Barón M, Feliu J, Espinosa E, García Girón C, Blanco E, Garrido P, Colmenarejo A, Ordóñez A, Moyano A, de la Gándara I, Zamora P; ONCOPAZ Cooperative Group. Comparison of two chemotherapeutic regimens--mitomycin + vindesine + cisplatin (MVP) vs mitomycin + ifosfamide + cisplatin (MIP)--in advanced non-small-cell lung cancer. Ann Oncol. 1994 Apr;5(4):323-7. [https://doi.org/10.1093/oxfordjournals.annonc.a058834 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8075028/ PubMed]
-# Gridelli C, Perrone F, Palmeri S, D'Aprile M, Cognetti F, Rossi A, Gebbia V, Pepe R, Veltri E, Airoma G, Russo A, Incoronato P, Scinto AF, Palazzolo G, Natali M, Leonardi V, Gallo C, De Placido S, Bianco AR; GOSCI. Mitomycin C plus vindesine plus etoposide (MEV) versus mitomycin C plus vindesine plus cisplatin (MVP) in stage IV non-small-cell lung cancer: A phase III multicentre randomised trial. Ann Oncol. 1996 Oct;7(8):821-6. [https://doi.org/10.1093/oxfordjournals.annonc.a010761 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8922196 PubMed]
+# Gridelli C, Perrone F, Palmeri S, D'Aprile M, Cognetti F, Rossi A, Gebbia V, Pepe R, Veltri E, Airoma G, Russo A, Incoronato P, Scinto AF, Palazzolo G, Natali M, Leonardi V, Gallo C, De Placido S, Bianco AR; GOSCI. Mitomycin C plus vindesine plus etoposide (MEV) versus mitomycin C plus vindesine plus cisplatin (MVP) in stage IV non-small-cell lung cancer: A phase III multicentre randomised trial. Ann Oncol. 1996 Oct;7(8):821-6. [https://doi.org/10.1093/oxfordjournals.annonc.a010761 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8922196/ PubMed]
-# Boni C, Savoldi L, Bisagni G, Ceci G, Crinò L, De Lisi V, Di Costanzo F, Lasagni L, Manenti AL, Moretti G, Rondini E, Sassi M, Zadro A; GOIRC. Bolus versus 5-day continuous infusion of cisplatin with mitomycin and vindesine in the treatment of advanced non-small cell lung cancer (NSCLC): a phase III prospective randomised trial of the Italian Oncology Group for Clinical Research (GOIRC). Eur J Cancer. 1998 Nov;34(12):1974-6. [https://www.ejcancer.com/article/S0959-8049(98)00231-7/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/10023325 PubMed]
+# Boni C, Savoldi L, Bisagni G, Ceci G, Crinò L, De Lisi V, Di Costanzo F, Lasagni L, Manenti AL, Moretti G, Rondini E, Sassi M, Zadro A; GOIRC. Bolus versus 5-day continuous infusion of cisplatin with mitomycin and vindesine in the treatment of advanced non-small cell lung cancer (NSCLC): a phase III prospective randomised trial of the Italian Oncology Group for Clinical Research (GOIRC). Eur J Cancer. 1998 Nov;34(12):1974-6. [https://doi.org/10.1016/s0959-8049(98)00231-7 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10023325/ PubMed]
-# Jelić S, Mitrović L, Radosavljević D, Elezar E, Babović N, Kovcin V, Tomasević Z, Kovacević S, Gavrilović D, Radulović S. Survival advantage for carboplatin substituting cisplatin in combination with vindesine and mitomycin C for stage IIIB and IV squamous-cell bronchogenic carcinoma: a randomized phase III study. Lung Cancer. 2001 Oct;34(1):1-13. [https://www.lungcancerjournal.info/article/S0169-5002(01)00239-2/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/11557107 PubMed]
+# Jelić S, Mitrović L, Radosavljević D, Elezar E, Babović N, Kovcin V, Tomasević Z, Kovacević S, Gavrilović D, Radulović S. Survival advantage for carboplatin substituting cisplatin in combination with vindesine and mitomycin C for stage IIIB and IV squamous-cell bronchogenic carcinoma: a randomized phase III study. Lung Cancer. 2001 Oct;34(1):1-13. [https://doi.org/10.1016/s0169-5002(01)00239-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11557107/ PubMed]
 ==Paclitaxel monotherapy {{#subobject:a87044|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#ee6b6e">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen variant #1, 100 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:866dac|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 900: / Line 1,223: @@
 |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409832/ Comella et al. 2004 (SICOG 9909)]
 |rowspan=2|1999-2003
-|rowspan=2 style="background-color:#1a9851"|Phase III (E-de-esc)
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-de-esc)
 |1. [[Non-small_cell_lung_cancer#Gemcitabine_monotherapy|Gemcitabine]]
 |style="background-color:#d3d3d3"|Not reported
 |-
 |2. [[Non-small_cell_lung_cancer#Gemcitabine_.26_Paclitaxel|GT]]<br> 3. [[Non-small_cell_lung_cancer#Gemcitabine_.26_Vinorelbine|GV]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
+| style="background-color:#fc8d59" |Seems to have inferior OS (primary endpoint)
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Paclitaxel (Taxol)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 '''28-day cycle for up to 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen variant #2, 200 mg/m<sup>2</sup> q3wk {{#subobject:5e38ca|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://academic.oup.com/jnci/article/92/13/1074/2909527 Ranson et al. 2000]
+|[https://doi.org/10.1093/jnci/92.13.1074 Ranson et al. 2000]
 |1995-1997
-|style="background-color:#1a9851"|Phase III (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-esc)
 |[[#Best_supportive_care|Best supportive care]]
 | style="background-color:#91cf60" |Seems to have superior OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1
 '''21-day cycles'''
+</div></div>
 ===References===
-# Ranson M, Davidson N, Nicolson M, Falk S, Carmichael J, Lopez P, Anderson H, Gustafson N, Jeynes A, Gallant G, Washington T, Thatcher N. Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 2000 Jul 5;92(13):1074-80. [https://academic.oup.com/jnci/article/92/13/1074/2909527 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10880550 PubMed]
+# Ranson M, Davidson N, Nicolson M, Falk S, Carmichael J, Lopez P, Anderson H, Gustafson N, Jeynes A, Gallant G, Washington T, Thatcher N. Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 2000 Jul 5;92(13):1074-80. [https://doi.org/10.1093/jnci/92.13.1074 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10880550/ PubMed]
-# '''SICOG 9909:''' Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, Cioffi R. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer. 2004 Aug 2;91(3):489-97. [https://www.nature.com/articles/6602011 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409832/ link to PMC article]  '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/15266334 PubMed]
+# '''SICOG 9909:''' Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, Cioffi R. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer. 2004 Aug 2;91(3):489-97. [https://doi.org/10.1038/sj.bjc.6602011 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409832/ link to PMC article]  '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15266334/ PubMed]
 ==Vindesine monotherapy {{#subobject:f9f7b9|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#ee6b6e">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:d123895|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 952: / Line 1,272: @@
 |[https://doi.org/10.1200/JCO.1986.4.7.1037 Einhorn et al. 1986]
 |1982-1984
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|1. Cisplatin & Vindesine<br> 2. Cisplatin, Mitomycin, Vindesine
+|1. [[#Cisplatin_.26_Vindesine|Cisplatin & Vindesine]]<br>2. [[#MVP_.28Vindesine.29|MVP]]
-|style="background-color:#ffffbf"|Seems not superior
+|style="background-color:#ffffbf"|Did not meet endpoint of OS
 |-
 |[https://doi.org/10.1093/oxfordjournals.annonc.a010760 Furuse et al. 1996]
 |1991-1993
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|Vinorelbine
+|[[#Vinorelbine_monotherapy|Vinorelbine]]
 | style="background-color:#d73027" |Inferior ORR
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Vindesine (Eldisine)]]
+*[[Vindesine (Eldisine)]] as follows:
+**Cycle 1: 3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+**Cycle 2 onwards: 3 mg/m<sup>2</sup> IV once per day on days 1 & 15
+'''28-day cycles'''
+</div></div>
 ===References===
-# Einhorn LH, Loehrer PJ, Williams SD, Meyers S, Gabrys T, Nattan SR, Woodburn R, Drasga R, Songer J, Fisher W, Stephens D, Hui S. Random prospective study of vindesine versus vindesine plus high-dose cisplatin versus vindesine plus cisplatin plus mitomycin C in advanced non-small-cell lung cancer. J Clin Oncol. 1986 Jul;4(7):1037-43. [https://doi.org/10.1200/JCO.1986.4.7.1037 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3088219 PubMed]
+# Einhorn LH, Loehrer PJ, Williams SD, Meyers S, Gabrys T, Nattan SR, Woodburn R, Drasga R, Songer J, Fisher W, Stephens D, Hui S. Random prospective study of vindesine versus vindesine plus high-dose cisplatin versus vindesine plus cisplatin plus mitomycin C in advanced non-small-cell lung cancer. J Clin Oncol. 1986 Jul;4(7):1037-43. [https://doi.org/10.1200/JCO.1986.4.7.1037 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/3088219/ PubMed]
-# Furuse K, Fukuoka M, Kuba M, Yamori S, Nakai Y, Negoro S, Katagami N, Takada Y, Kinuwaki E, Kawahara M, Kubota K, Sakuma A, Niitani H; Japan Vinorelbine Lung Cancer Cooperative Study Group. Randomized study of vinorelbine (VRB) versus vindesine (VDS) in previously untreated stage IIIB or IV non-small-cell lung cancer (NSCLC). Ann Oncol. 1996 Oct;7(8):815-20. [https://doi.org/10.1093/oxfordjournals.annonc.a010760 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8922195 PubMed]
+# Furuse K, Fukuoka M, Kuba M, Yamori S, Nakai Y, Negoro S, Katagami N, Takada Y, Kinuwaki E, Kawahara M, Kubota K, Sakuma A, Niitani H; Japan Vinorelbine Lung Cancer Cooperative Study Group. Randomized study of vinorelbine (VRB) versus vindesine (VDS) in previously untreated stage IIIB or IV non-small-cell lung cancer (NSCLC). Ann Oncol. 1996 Oct;7(8):815-20. [https://doi.org/10.1093/oxfordjournals.annonc.a010760 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8922195/ PubMed]
 ==Vinorelbine monotherapy {{#subobject:f8gub9|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #1, 25 mg/m<sup>2</sup>/week {{#subobject:d25fc5|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1093/oxfordjournals.annonc.a010760 Furuse et al. 1996]
+|1991-1993
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+|[[#Vindesine_monotherapy|Vindesine]]
+| style="background-color:#1a9850" |Superior ORR
 |-
-|[[#top|back to top]]
 |}
-===Regimen {{#subobject:dab895|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once on day 1
+'''7-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #2, 30 mg/m<sup>2</sup>/week {{#subobject:dab895|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1093/oxfordjournals.annonc.a058687 Depierre et al. 1994]
+|1989-1991
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine_.28CVb.29_3|CVb]]
+| style="background-color:#d73027" |Inferior TTP
+|-
+| rowspan="2" |[https://doi.org/10.1200/JCO.1994.12.2.360 Le Chevalier et al. 1994]
+| rowspan="2" |1989-1991
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-de-esc)
+|1. [[#Cisplatin_.26_Vindesine|Cisplatin & Vindesine]]
+| style="background-color:#d3d3d3" |Not reported
+|-
+|2. [[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine_.28CVb.29_3|CVb]]
+| style="background-color:#d73027" |Inferior OS
 |-
 |[https://doi.org/10.1200/JCO.1996.14.10.2774 Crawford et al. 1996]
 |1990-1992
 |style="background-color:#1a9851"|Randomized (E-RT-switch-ic)
-|FULV
+|[[#FULV|FULV]]
 | style="background-color:#91cf60" |Seems to have superior OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Vinorelbine (Navelbine)]]
+*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once on day 1
+'''7-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #3, 30 mg/m<sup>2</sup>, 2 out of 3 weeks {{#subobject:2cz895|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/s0169-5002(01)00392-0 Frasci et al. 2001]
+|Not reported
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[Non-small_cell_lung_cancer#Gemcitabine_.26_Vinorelbine|Gemcitabine & Vinorelbine]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|}
+''Note: To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
+'''21-day cycles'''
+</div></div>
 ===References===
-# Crawford J, O'Rourke M, Schiller JH, Spiridonidis CH, Yanovich S, Ozer H, Langleben A, Hutchins L, Koletsky A, Clamon G, Burman S, White R, Hohneker J. Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer. J Clin Oncol. 1996 Oct;14(10):2774-84. Erratum in: J Clin Oncol 1996 Dec;14(12):3175. Spiridonitis CH [corrected to Spiridonidis CH]. [https://doi.org/10.1200/JCO.1996.14.10.2774 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8874339 PubMed]
+#Depierre A, Chastang C, Quoix E, Lebeau B, Blanchon F, Paillot N, Lemarie E, Milleron B, Moro D, Clavier J, Herman D, Tuchais E, Jacoulet P, Brechot JM, Cordier JF, Solal-Celigny P, Badri N, Besenval M. Vinorelbine versus vinorelbine plus cisplatin in advanced non-small cell lung cancer: a randomized trial. Ann Oncol. 1994 Jan;5(1):37-42. [https://doi.org/10.1093/oxfordjournals.annonc.a058687 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8172790/ PubMed]
+#Le Chevalier T, Brisgand D, Douillard JY, Pujol JL, Alberola V, Monnier A, Riviere A, Lianes P, Chomy P, Cigolari S, Gottfried M, Ruffle P, Panizo A, Gaspard MH, Ravaioli A, Besenval M, Besson F, Martinez A, Berthaud P, Tursz T. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients. J Clin Oncol. 1994 Feb;12(2):360-7. [https://doi.org/10.1200/JCO.1994.12.2.360 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8113844/ PubMed]
+# Crawford J, O'Rourke M, Schiller JH, Spiridonidis CH, Yanovich S, Ozer H, Langleben A, Hutchins L, Koletsky A, Clamon G, Burman S, White R, Hohneker J. Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer. J Clin Oncol. 1996 Oct;14(10):2774-84. Erratum in: J Clin Oncol 1996 Dec;14(12):3175. Spiridonitis CH [corrected to Spiridonidis CH]. [https://doi.org/10.1200/JCO.1996.14.10.2774 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8874339/ PubMed]
+# Furuse K, Fukuoka M, Kuba M, Yamori S, Nakai Y, Negoro S, Katagami N, Takada Y, Kinuwaki E, Kawahara M, Kubota K, Sakuma A, Niitani H; Japan Vinorelbine Lung Cancer Cooperative Study Group. Randomized study of vinorelbine (VRB) versus vindesine (VDS) in previously untreated stage IIIB or IV non-small-cell lung cancer (NSCLC). Ann Oncol. 1996 Oct;7(8):815-20. [https://doi.org/10.1093/oxfordjournals.annonc.a010760 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8922195/ PubMed]
+#Frasci G, Lorusso V, Panza N, Comella P, Nicolella G, Bianco A, DeCataldis G, Belli M, Iannelli N, Massidda B, Mascia V, Comella G, De Lena M; Southern Italy Cooperative Oncology Group. Gemcitabine plus vinorelbine yields better survival outcome than vinorelbine alone in elderly patients with advanced non-small cell lung cancer: a Southern Italy Cooperative Oncology Group (SICOG) phase III trial. Lung Cancer. 2001 Dec;34 Suppl 4:S65-9. [https://doi.org/10.1016/s0169-5002(01)00392-0 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11742706/ PubMed]
-==VIP {{#subobject:e6f7b9|Regimen=1}}==
+==VeIP {{#subobject:e6f7b9|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+VeIP: '''<u>Ve</u>'''lban (Vinblastine), '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
-|-
+<br>VIP: '''<u>V</u>'''inblastine, '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
-|[[#top|back to top]]
+<div class="toccolours" style="background-color:#ee6b6e">
-|}
-VIP: '''<u>V</u>'''inblastine, '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
 ===Regimen {{#subobject:d00565|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 1,010: / Line 1,395: @@
 |[https://doi.org/10.1093/oxfordjournals.annonc.a010642 Kosmidis et al. 1996a]
 |1992-1994
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|VIP-16
+|[[#VIP-16_999|VIP-16]]
-|style="background-color:#ffffbf"|Seems not superior
+|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Vinblastine (Velban)]]
+*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV once on day 1
-*[[Ifosfamide (Ifex)]]
+*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV once on day 1
-*[[Cisplatin (Platinol)]]
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycles'''
+</div></div>
 ===References===
-# Kosmidis P, Mylonakis N, Fountzilas G, Pavlidis N, Samantas E, Karabelis A, Kattis K, Skarlos D; HeCOG. A prospective randomized phase III study in non-small-cell lung cancer comparing cisplatin, ifosfamide, vinblastine (VIP) versus cisplatin, ifosfamide and etoposide (VIP-16). Ann Oncol. 1996 Jul;7(5):517-20. [https://doi.org/10.1093/oxfordjournals.annonc.a010642 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8839908 PubMed]
+# Kosmidis P, Mylonakis N, Fountzilas G, Pavlidis N, Samantas E, Karabelis A, Kattis K, Skarlos D; HeCOG. A prospective randomized phase III study in non-small-cell lung cancer comparing cisplatin, ifosfamide, vinblastine (VIP) versus cisplatin, ifosfamide and etoposide (VIP-16). Ann Oncol. 1996 Jul;7(5):517-20. [https://doi.org/10.1093/oxfordjournals.annonc.a010642 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8839908/ PubMed]
 =Maintenance after first-line therapy=
 ==Erlotinib monotherapy {{#subobject:096cdf|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#ee6b6e">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:16398e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70112-1/fulltext Cappuzzo et al. 2010 (SATURN)]
+|[https://doi.org/10.1016/S1470-2045(10)70112-1 Cappuzzo et al. 2010 (SATURN)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-74-1 <span style="color:white;">ESMO-MCBS (1)</span>]'''
+|-
+|} -->
 |2005-2008
-|style="background-color:#1a9851"|Phase III (E-RT-esc)
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 |[[Non-small_cell_lung_cancer#Placebo_4|Placebo]]
-|style="background-color:#1a9850"|Superior PFS
+|style="background-color:#1a9850"|Superior PFS (co-primary endpoint)<br>Median PFS: 12.3 vs 11.1 weeks<br>(HR 0.71, 95% CI 0.62-0.82)
 |-
 |rowspan=2|[https://doi.org/10.1200/JCO.2011.39.9782 Pérol et al. 2012 (IFCT-GFPC 0502)]
 |rowspan=2|2006-2009
-|rowspan=2 style="background-color:#1a9851"|Phase III (E-esc)
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
 |1. [[Non-small_cell_lung_cancer#Gemcitabine_monotherapy_2|Gemcitabine]]
 |style="background-color:#d3d3d3"|Not reported
 |-
 |2. [[Non-small_cell_lung_cancer#Observation_3|Observation]]
-|style="background-color:#1a9850"|Superior PFS
+|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 2.9 vs 1.9 mo<br>(HR 0.69, 95% CI 0.54-0.88)
 |-
-|[http://www.lungcancerjournal.info/article/S0169-5002(16)30504-9/fulltext Cicènas et al. 2016 (IUNO)]
+|[https://doi.org/10.1016/j.lungcan.2016.10.007 Cicènas et al. 2016 (IUNO)]
 |2011-2014
-|style="background-color:#1a9851"|Phase III (E-switch-ic)
+|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
 |[[Complex_multipart_regimens#IUNO|See link]]
 | style="background-color:#ffffbf" |[[Complex_multipart_regimens#IUNO|See link]]
@@ Line 1,061: / Line 1,448: @@
 |}
 ''Note: while SATURN was technically a positive study for erlotinib, the median PFS gain was 1.2 weeks. This study was the basis of an FDA approval in 2010, which was later revised after the results of IUNO became available. The trials included here did not require EGFR mutation as a condition for enrollment.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*SATURN and IUNO: 4 cycles of platinum-doublet therapy
+*SATURN and IUNO: First-line [[Regimen_classes#Platinum_doublet|platinum-doublet therapy]] x 4
-*IFCT-GFPC 0502: [[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]] x 4
+*IFCT-GFPC 0502: First-line [[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_.28GC.29_3|GC]] x 4
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Erlotinib (Tarceva)]] 150 mg PO once per day
+*[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 1 to 28
+'''28-day cycles'''
-'''Continued indefinitely'''
+</div></div>
 ===References===
-# '''SATURN:''' Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczésna A, Juhász E, Esteban E, Molinier O, Brugger W, Melezínek I, Klingelschmitt G, Klughammer B, Giaccone G; SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010 Jun;11(6):521-9. Epub 2010 May 20. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70112-1/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/20493771 PubMed] NCT00556712
+# '''SATURN:''' Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczésna A, Juhász E, Esteban E, Molinier O, Brugger W, Melezínek I, Klingelschmitt G, Klughammer B, Giaccone G; SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010 Jun;11(6):521-9. Epub 2010 May 20. [https://doi.org/10.1016/S1470-2045(10)70112-1 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20493771/ PubMed] [https://clinicaltrials.gov/study/NCT00556712 NCT00556712]
-# '''IFCT-GFPC 0502:''' Pérol M, Chouaid C, Pérol D, Barlési F, Gervais R, Westeel V, Crequit J, Léna H, Vergnenègre A, Zalcman G, Monnet I, Le Caer H, Fournel P, Falchero L, Poudenx M, Vaylet F, Ségura-Ferlay C, Devouassoux-Shisheboran M, Taron M, Milleron B. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2012 Oct 1;30(28):3516-24. Epub 2012 Sep 4. [https://doi.org/10.1200/JCO.2011.39.9782 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/22949150 PubMed] NCT00300586
+# '''IFCT-GFPC 0502:''' Pérol M, Chouaid C, Pérol D, Barlési F, Gervais R, Westeel V, Crequit J, Léna H, Vergnenègre A, Zalcman G, Monnet I, Le Caer H, Fournel P, Falchero L, Poudenx M, Vaylet F, Ségura-Ferlay C, Devouassoux-Shisheboran M, Taron M, Milleron B. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2012 Oct 1;30(28):3516-24. Epub 2012 Sep 4. [https://doi.org/10.1200/JCO.2011.39.9782 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22949150/ PubMed] [https://clinicaltrials.gov/study/NCT00300586 NCT00300586]
-# '''IUNO:''' Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. [http://www.lungcancerjournal.info/article/S0169-5002(16)30504-9/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/27987585 PubMed] NCT01328951
+# '''IUNO:''' Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. [https://doi.org/10.1016/j.lungcan.2016.10.007 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27987585/ PubMed] [https://clinicaltrials.gov/study/NCT01328951 NCT01328951]
 =Advanced or metastatic disease, subsequent lines of therapy=
 ==Erlotinib monotherapy {{#subobject:c3c726|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#ee6b6e">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:d27efc|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa050753 Shepherd et al. 2005 (NCIC-CTG BR.21)]
+|[https://doi.org/10.1056/NEJMoa050753 Shepherd et al. 2005 (NCIC-CTG BR.21)]
 |2001-2003
-|style="background-color:#1a9851"|Phase III (E-RT-esc)
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 |[[Non-small_cell_lung_cancer#Placebo_4|Placebo]]
-|style="background-color:#1a9850"|Superior OS<br>Median OS: 6.7 vs 4.7 mo<br>(aHR 0.70, 95% CI 0.58-0.85)
+|style="background-color:#1a9850"|Superior OS (primary endpoint)<br>Median OS: 6.7 vs 4.7 mo<br>(aHR 0.70, 95% CI 0.58-0.85)
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134127/ Herbst et al. 2011 (BeTa)]
 |2005-2008
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|Erlotinib & Bevacizumab
+|[[#Erlotinib_.26_Bevacizumab_999|Erlotinib & Bevacizumab]]
 |style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 |-
 |[https://doi.org/10.1200/JCO.2010.28.5981 Natale et al. 2011 (ZEST)]
-|2006-2007
+|2006-10 to 2007-11
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|Vandetanib
+|[[#Vandetanib_monotherapy_999|Vandetanib]]
 |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70385-0/fulltext Ciuleanu et al. 2012 (TITAN)]
+|[https://doi.org/10.1016/S1470-2045(11)70385-0 Ciuleanu et al. 2012 (TITAN)]
 |2006-2010
-|style="background-color:#1a9851"|Phase III (E-switch-ooc)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
-|Investigator's choice of:<br> 1. [[Non-small_cell_lung_cancer#Docetaxel_monotherapy_3|Docetaxel]]<br> 2. [[Non-small_cell_lung_cancer#Pemetrexed_monotherapy_3|Pemetrexed]]
+|Investigator's choice of:<br>1a. [[Non-small_cell_lung_cancer#Docetaxel_monotherapy_3|Docetaxel]]<br>1b. [[Non-small_cell_lung_cancer#Pemetrexed_monotherapy_3|Pemetrexed]]
 |style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 |-
-|[https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.28132 Karampeazis et al. 2013 (CT/06.05)]
+|[https://doi.org/10.1002/cncr.28132 Karampeazis et al. 2013 (CT/06.05)]
 |2006-2010
-|style="background-color:#1a9851"|Phase III (E-switch-ooc)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 |[[Non-small_cell_lung_cancer#Pemetrexed_monotherapy_3|Pemetrexed]]
 |style="background-color:#ffffbf"|Did not meet primary endpoint of TTP
@@ Line 1,120: / Line 1,506: @@
 |[https://doi.org/10.1200/JCO.2011.39.2993 Scagliotti et al. 2012 (SUN 1087)]
 |2007-2009
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[Stub#Erlotinib_.26_Sunitinib|Erlotinib & Sunitinib]]
 |style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70310-3/fulltext Garassino et al. 2013 (TAILOR<sub>NSCLC</sub>)]
+|[https://doi.org/10.1016/S1470-2045(13)70310-3 Garassino et al. 2013 (TAILOR<sub>NSCLC</sub>)]
 |2007-2012
-|style="background-color:#1a9851"|Phase III (E-switch-ooc)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 |[[Non-small_cell_lung_cancer#Docetaxel_monotherapy_3|Docetaxel]]
-|style="background-color:#fc8d59"|Seems to have inferior OS
+|style="background-color:#fc8d59"|Seems to have inferior OS (primary endpoint)<br>Median OS: 5.4 vs 8.2 mo<br>(aHR 1.37, 95% CI 1.00-1.89)
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321098/ Ramalingam et al. 2012 (A7471028)]
 |2008-2009
-|style="background-color:#1a9851"|Randomized Phase II (C)
+|style="background-color:#1a9851"|Randomized Phase 2 (C)
-|Dacomitinib
+|[[#Dacomitinib_monotherapy_999|Dacomitinib]]
 |style="background-color:#fc8d59"|Seems to have inferior PFS
 |-
 |[https://doi.org/10.1093/annonc/mdu517 Scagliotti et al. 2015 (ADVIGO 1018)]
 |2008-2010
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[Stub#Erlotinib_.26_Figitumumab|Erlotinib & Figitumumab]]
 |style="background-color:#ffffbf"|Did not meet primary endpoint of OS
@@ Line 1,144: / Line 1,530: @@
 |[https://doi.org/10.1200/JCO.2013.52.4694 Kawaguchi et al. 2014 (DELTA<sub>NSCLC</sub>)]
 |2009-2012
-|style="background-color:#1a9851"|Phase III (E-switch-ooc)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 |[[Non-small_cell_lung_cancer#Docetaxel_monotherapy_3|Docetaxel]]
-| style="background-color:#fee08b" |Might have inferior PFS
+| style="background-color:#fee08b" |Might have inferior PFS (primary endpoint)
 |-
 |[https://doi.org/10.1200/jco.2015.63.4154 Urata et al. 2016 (WJOG 5108L)]
 |2009-2012
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[Non-small_cell_lung_cancer#Gefitinib_monotherapy_2|Gefitinib]]
 |style="background-color:#ffffbf"|Inconclusive whether non-inferior PFS
 |-
-|[http://www.lungcancerjournal.info/article/S0169-5002(16)30377-4/fulltext Smit et al. 2016 (CurrentS)]
+|[https://doi.org/10.1016/j.lungcan.2016.06.019 Smit et al. 2016 (CurrentS)]
-|2010-NR
+|2010 to not reported
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[#Erlotinib_monotherapy_2|Erlotinib]]; high-dose
 |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
@@ Line 1,162: / Line 1,548: @@
 |[https://doi.org/10.1016/j.biopha.2017.02.097 Wang et al. 2017a]
 |2010-2014
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|Erlotinib, Bevacizumab, Panitumumab
+|[[#Erlotinib.2C_Bevacizumab.2C_Panitumumab_888|Erlotinib, Bevacizumab, Panitumumab]]
 |style="background-color:#fc8d59"|Seems to have inferior OS
 |-
-|[https://doi.org/10.1093/annonc/mdv288 Yoshioka et al. 2015 (ATTENTION)]
+|[https://doi.org/10.1200/JCO.2014.60.7317 Scagliotti et al. 2015 (MARQUEE)]
-|2011-2012
+|2011-01 to 2012-07
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[Stub#Erlotinib_.26_Tivantinib|Erlotinib & Tivantinib]]
 |style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 |-
-|[https://doi.org/10.1200/JCO.2014.60.7317 Scagliotti et al. 2015 (MARQUEE)]
+|[https://doi.org/10.1093/annonc/mdv288 Yoshioka et al. 2015 (ATTENTION)]
-|2011-2012
+|2011-08 to 2012-10
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[Stub#Erlotinib_.26_Tivantinib|Erlotinib & Tivantinib]]
 |style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70452-8/abstract Ramalingam et al. 2014 (ARCHER 1009)]
+|[https://doi.org/10.1016/S1470-2045(14)70452-8 Ramalingam et al. 2014 (ARCHER 1009)]
 |2011-2013
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|Dacomitinib
+|[[#Dacomitinib_monotherapy_999|Dacomitinib]]
 |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
 |-
-|[http://www.lungcancerjournal.info/article/S0169-5002(16)30504-9/fulltext Cicènas et al. 2016 (IUNO)]
+|[https://doi.org/10.1016/j.lungcan.2016.10.007 Cicènas et al. 2016 (IUNO)]
 |2011-2014
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 |[[Complex_multipart_regimens#IUNO|See link]]
 |style="background-color:#ffffbf"|[[Complex_multipart_regimens#IUNO|See link]]
@@ Line 1,192: / Line 1,578: @@
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440713 Gridelli et al. 2018 (AvaALL)]
 |2011-2015
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|Investigator's choice of:<br> 1. Docetaxel & Bevacizumab<br> 2. Erlotinib & Bevacizumab<br> 3. Pemetrexed & Bevacizumab
+|Investigator's choice of:<br>1a. [[#Docetaxel_.26_Bevacizumab_999|Docetaxel & Bevacizumab]]<br>1b. [[#Erlotinib_.26_Bevacizumab_999|Erlotinib & Bevacizumab]]<br>1c. [[#Pemetrexed_.26_Bevacizumab_999|Pemetrexed & Bevacizumab]]
 |style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 |-
 |[https://doi.org/10.1200/JCO.2016.69.2160 Spigel et al. 2016 (METLung)]
-|2012-2013
+|2012-01 to 2013-08
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[Stub#Erlotinib_.26_Onartuzumab|Erlotinib & Onartuzumab]]
 |style="background-color:#d9ef8b"|Might have superior OS
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00006-6/fulltext Soria et al. 2015 (LUX-Lung 8)]
+|[https://doi.org/10.1016/S1470-2045(15)00006-6 Soria et al. 2015 (LUX-Lung 8)]
 |2012-2014
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
 |[[Non-small_cell_lung_cancer#Afatinib_monotherapy|Afatinib]]
-|style="background-color:#d73027"|Inferior OS
+| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 |-
-|rowspan=2|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30561-7/fulltext Neal et al. 2016 (ECOG-ACRIN 1512)]
+|rowspan=2|[https://doi.org/10.1016/S1470-2045(16)30561-7 Neal et al. 2016 (ECOG-ACRIN 1512)]
 |rowspan=2|2013-2014
-|rowspan=2 style="background-color:#1a9851"|Randomized Phase II (C)
+|rowspan=2 style="background-color:#1a9851"|Randomized Phase 2 (C)
 |1. [[Non-small_cell_lung_cancer#Cabozantinib_monotherapy|Cabozantinib]]
 |style="background-color:#d73027"|Inferior PFS
@@ Line 1,217: / Line 1,603: @@
 |style="background-color:#d73027"|Inferior PFS
 |-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7649422/ Goldman et al. 2020 (JUNIPER)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7649422/ Goldman et al. 2020 (JUNIPER)]
 |2014-2017
-|style="background-color:#1a9851"|Phase III (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|Abemaciclib
+|[[#Abemaciclib_monotherapy_999|Abemaciclib]]
 |style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 |-
 |}
+''<sup>1</sup>Reported efficacy is based on the 2021 update.''<br>
 ''Note: the trials included here did not require EGFR mutation as a condition for enrollment. Given the FDA limitation on use in this setting issued in 2016, these regimens have been moved to the historical page. Note that there is another trial named TAILOR in colorectal cancer and another trial named DELTA in indolent lymphoma.''
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *JUNIPER: KRAS G12 or G13 mutation
-====Preceding treatment====
+</div>
-*IUNO: [[Non-small_cell_lung_cancer#Placebo_4|Placebo]]
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Erlotinib (Tarceva)]] 150 mg PO once per day
+*[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 1 to 28
+'''28-day cycles'''
-'''Continued indefinitely'''
+</div></div>
 ===References===
-# '''NCIC-CTG BR.21:''' Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. [https://www.nejm.org/doi/full/10.1056/NEJMoa050753 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/16014882 PubMed]
+# '''NCIC-CTG BR.21:''' Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. [https://doi.org/10.1056/NEJMoa050753 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16014882/ PubMed] [https://clinicaltrials.gov/study/NCT00036647 NCT00036647]
 <!-- Presented at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL; 13th Annual World Congress on Lung Cancer, July 31-August 4, 2009, San Francisco, CA; and Joint 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology, September 20-24, 2009, Berlin, Germany. -->
-# '''ZEST:''' Natale RB, Thongprasert S, Greco FA, Thomas M, Tsai CM, Sunpaweravong P, Ferry D, Mulatero C, Whorf R, Thompson J, Barlesi F, Langmuir P, Gogov S, Rowbottom JA, Goss GD. Phase III trial of vandetanib compared with erlotinib in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol. 2011 Mar 10;29(8):1059-66. Epub 2011 Jan 31. [https://doi.org/10.1200/JCO.2010.28.5981 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/21282542 PubMed] NCT00364351
+# '''ZEST:''' Natale RB, Thongprasert S, Greco FA, Thomas M, Tsai CM, Sunpaweravong P, Ferry D, Mulatero C, Whorf R, Thompson J, Barlesi F, Langmuir P, Gogov S, Rowbottom JA, Goss GD. Phase III trial of vandetanib compared with erlotinib in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol. 2011 Mar 10;29(8):1059-66. Epub 2011 Jan 31. [https://doi.org/10.1200/JCO.2010.28.5981 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21282542/ PubMed] [https://clinicaltrials.gov/study/NCT00364351 NCT00364351]
 ## '''Dataset:''' [https://www.projectdatasphere.org/projectdatasphere/html/content/164 Project Data Sphere]
-# '''BeTa:''' Herbst RS, Ansari R, Bustin F, Flynn P, Hart L, Otterson GA, Vlahovic G, Soh CH, O'Connor P, Hainsworth J. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. Lancet. 2011 May 28;377(9780):1846-54. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60545-X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134127/ link to PMC article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/21621716 PubMed] NCT00130728
+# '''BeTa:''' Herbst RS, Ansari R, Bustin F, Flynn P, Hart L, Otterson GA, Vlahovic G, Soh CH, O'Connor P, Hainsworth J. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. Lancet. 2011 May 28;377(9780):1846-54. [https://doi.org/10.1016/S0140-6736(11)60545-X link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134127/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21621716/ PubMed] [https://clinicaltrials.gov/study/NCT00130728 NCT00130728]
-# '''TITAN:''' Ciuleanu T, Stelmakh L, Cicenas S, Miliauskas S, Grigorescu AC, Hillenbach C, Johannsdottir HK, Klughammer B, Gonzalez EE. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol. 2012 Mar;13(3):300-8. Epub 2012 Jan 24. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70385-0/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/22277837 PubMed]
+# '''TITAN:''' Ciuleanu T, Stelmakh L, Cicenas S, Miliauskas S, Grigorescu AC, Hillenbach C, Johannsdottir HK, Klughammer B, Gonzalez EE. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol. 2012 Mar;13(3):300-8. Epub 2012 Jan 24. [https://doi.org/10.1016/S1470-2045(11)70385-0 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22277837/ PubMed] [https://clinicaltrials.gov/study/NCT00556322 NCT00556322]
 <!-- Presented previously, in part, at the European Society for Medical Oncology Congress, Milan, Italy, October 8-12, 2010; Asia-Pacific Lung Cancer Conference, Seoul, Korea, December 2-4, 2010; and the Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL, December 9-11, 2010. -->
-# '''SUN 1087:''' Scagliotti GV, Krzakowski M, Szczesna A, Strausz J, Makhson A, Reck M, Wierzbicki RF, Albert I, Thomas M, Miziara JE, Papai ZS, Karaseva N, Thongprasert S, Portulas ED, von Pawel J, Zhang K, Selaru P, Tye L, Chao RC, Govindan R. Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer: a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2070-8. Epub 2012 May 7. [https://doi.org/10.1200/JCO.2011.39.2993 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/22564989 PubMed] NCT00457392
+# '''SUN 1087:''' Scagliotti GV, Krzakowski M, Szczesna A, Strausz J, Makhson A, Reck M, Wierzbicki RF, Albert I, Thomas M, Miziara JE, Papai ZS, Karaseva N, Thongprasert S, Portulas ED, von Pawel J, Zhang K, Selaru P, Tye L, Chao RC, Govindan R. Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer: a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2070-8. Epub 2012 May 7. [https://doi.org/10.1200/JCO.2011.39.2993 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22564989/ PubMed] [https://clinicaltrials.gov/study/NCT00457392 NCT00457392]
 <!-- Presented in part at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL; the 35th Congress of the European Society for Medical Oncology, October 8-12, 2010, Milan, Italy; and the 14th World Conference on Lung Cancer, July 3-7, 2011, Amsterdam, the Netherlands. -->
-# '''A7471028:''' Ramalingam SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, Seog Heo D, Rosell R, Talbot DC, Frank R, Letrent SP, Ruiz-Garcia A, Taylor I, Liang JQ, Campbell AK, O'Connell J, Boyer M. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2012 Sep 20;30(27):3337-44. [https://doi.org/10.1200/JCO.2011.40.9433 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321098/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22753918 PubMed] NCT00769067
+# '''A7471028:''' Ramalingam SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, Seog Heo D, Rosell R, Talbot DC, Frank R, Letrent SP, Ruiz-Garcia A, Taylor I, Liang JQ, Campbell AK, O'Connell J, Boyer M. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2012 Sep 20;30(27):3337-44. Epub 2012 Jul 2. [https://doi.org/10.1200/JCO.2011.40.9433 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321098/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22753918/ PubMed] [https://clinicaltrials.gov/study/NCT00769067 NCT00769067]
-# '''CT/06.05:''' Karampeazis A, Voutsina A, Souglakos J, Kentepozidis N, Giassas S, Christofillakis C, Kotsakis A, Papakotoulas P, Rapti A, Agelidou M, Agelaki S, Vamvakas L, Samonis G, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Pemetrexed versus erlotinib in pretreated patients with advanced non-small cell lung cancer: a Hellenic Oncology Research Group (HORG) randomized phase 3 study. Cancer. 2013 Aug 1;119(15):2754-64. Epub 2013 May 9. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.28132 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/23661337 PubMed]
+# '''CT/06.05:''' Karampeazis A, Voutsina A, Souglakos J, Kentepozidis N, Giassas S, Christofillakis C, Kotsakis A, Papakotoulas P, Rapti A, Agelidou M, Agelaki S, Vamvakas L, Samonis G, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Pemetrexed versus erlotinib in pretreated patients with advanced non-small cell lung cancer: a Hellenic Oncology Research Group (HORG) randomized phase 3 study. Cancer. 2013 Aug 1;119(15):2754-64. Epub 2013 May 9. [https://doi.org/10.1002/cncr.28132 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23661337/ PubMed] [https://clinicaltrials.gov/study/NCT00440414 NCT00440414]
-# '''TAILOR:''' Garassino MC, Martelli O, Broggini M, Farina G, Veronese S, Rulli E, Bianchi F, Bettini A, Longo F, Moscetti L, Tomirotti M, Marabese M, Ganzinelli M, Lauricella C, Labianca R, Floriani I, Giaccone G, Torri V, Scanni A, Marsoni S; TAILOR trialists. Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol. 2013 Sep;14(10):981-8. Epub 2013 Jul 22. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70310-3/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/23883922 PubMed]
+# '''TAILOR<sub>NSCLC</sub>:''' Garassino MC, Martelli O, Broggini M, Farina G, Veronese S, Rulli E, Bianchi F, Bettini A, Longo F, Moscetti L, Tomirotti M, Marabese M, Ganzinelli M, Lauricella C, Labianca R, Floriani I, Giaccone G, Torri V, Scanni A, Marsoni S; TAILOR trialists. Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol. 2013 Sep;14(10):981-8. Epub 2013 Jul 22. [https://doi.org/10.1016/S1470-2045(13)70310-3 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23883922/ PubMed] [https://clinicaltrials.gov/study/NCT00637910 NCT00637910]
-# '''DELTA:''' Kawaguchi T, Ando M, Asami K, Okano Y, Fukuda M, Nakagawa H, Ibata H, Kozuki T, Endo T, Tamura A, Kamimura M, Sakamoto K, Yoshimi M, Soejima Y, Tomizawa Y, Isa S, Takada M, Saka H, Kubo A. Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol. 2014 Jun 20;32(18):1902-8. Epub 2014 May 19. [https://doi.org/10.1200/JCO.2013.52.4694 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/24841974 PubMed]
+# '''DELTA<sub>NSCLC</sub>:''' Kawaguchi T, Ando M, Asami K, Okano Y, Fukuda M, Nakagawa H, Ibata H, Kozuki T, Endo T, Tamura A, Kamimura M, Sakamoto K, Yoshimi M, Soejima Y, Tomizawa Y, Isa S, Takada M, Saka H, Kubo A. Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol. 2014 Jun 20;32(18):1902-8. Epub 2014 May 19. [https://doi.org/10.1200/JCO.2013.52.4694 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24841974/ PubMed]
-# '''ARCHER 1009:''' Ramalingam SS, Jänne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. Epub 2014 Oct 15.[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70452-8/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/25439691 PubMed] NCT01360554
+# '''ARCHER 1009:''' Ramalingam SS, Jänne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. Epub 2014 Oct 15.[https://doi.org/10.1016/S1470-2045(14)70452-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25439691/ PubMed] [https://clinicaltrials.gov/study/NCT01360554 NCT01360554]
-# '''ADVIGO 1018:''' Scagliotti GV, Bondarenko I, Blackhall F, Barlesi F, Hsia TC, Jassem J, Milanowski J, Popat S, Sanchez-Torres JM, Novello S, Benner RJ, Green S, Molpus K, Soria JC, Shepherd FA. Randomized, phase III trial of figitumumab in combination with erlotinib versus erlotinib alone in patients with nonadenocarcinoma nonsmall-cell lung cancer. Ann Oncol. 2015 Mar;26(3):497-504. Epub 2014 Nov 13. [https://doi.org/10.1093/annonc/mdu517 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25395283 PubMed] NCT00673049
+# '''ADVIGO 1018:''' Scagliotti GV, Bondarenko I, Blackhall F, Barlesi F, Hsia TC, Jassem J, Milanowski J, Popat S, Sanchez-Torres JM, Novello S, Benner RJ, Green S, Molpus K, Soria JC, Shepherd FA. Randomized, phase III trial of figitumumab in combination with erlotinib versus erlotinib alone in patients with nonadenocarcinoma nonsmall-cell lung cancer. Ann Oncol. 2015 Mar;26(3):497-504. Epub 2014 Nov 13. [https://doi.org/10.1093/annonc/mdu517 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25395283/ PubMed] [https://clinicaltrials.gov/study/NCT00673049 NCT00673049]
-# '''LUX-Lung 8:''' Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015 Aug;16(8):897-907. Epub 2015 Jul 5. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00006-6/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/26156651 PubMed] NCT01523587
+# '''LUX-Lung 8:''' Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015 Aug;16(8):897-907. Epub 2015 Jul 5. [https://doi.org/10.1016/S1470-2045(15)00006-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26156651/ PubMed] [https://clinicaltrials.gov/study/NCT01523587 NCT01523587]
-# '''ATTENTION:''' Yoshioka H, Azuma K, Yamamoto N, Takahashi T, Nishio M, Katakami N, Ahn MJ, Hirashima T, Maemondo M, Kim SW, Kurosaki M, Akinaga S, Park K, Tsai CM, Tamura T, Mitsudomi T, Nakagawa K. A randomized, double-blind, placebo-controlled, phase III trial of erlotinib with or without a c-Met inhibitor tivantinib (ARQ 197) in Asian patients with previously treated stage IIIB/IV nonsquamous nonsmall-cell lung cancer harboring wild-type epidermal growth factor receptor (ATTENTION study). Ann Oncol. 2015 Oct;26(10):2066-72. Epub 2015 Jul 7. [https://doi.org/10.1093/annonc/mdv288 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26153496 PubMed] NCT01377376
+##'''PRO analysis:''' Felip E, Hirsh V, Popat S, Cobo M, Fülöp A, Dayen C, Trigo JM, Gregg R, Waller CF, Soria JC, Goss GD, Gordon J, Wang B, Palmer M, Ehrnrooth E, Gadgeel SM. Symptom and Quality of Life Improvement in LUX-Lung 8, an Open-Label Phase III Study of Second-Line Afatinib Versus Erlotinib in Patients With Advanced Squamous Cell Carcinoma of the Lung After First-Line Platinum-Based Chemotherapy. Clin Lung Cancer. 2018 Jan;19(1):74-83.e11. Epub 2017 Jun 23. [https://doi.org/10.1016/j.cllc.2017.06.002 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28729180/ PubMed]
-# '''MARQUEE:''' Scagliotti G, von Pawel J, Novello S, Ramlau R, Favaretto A, Barlesi F, Akerley W, Orlov S, Santoro A, Spigel D, Hirsh V, Shepherd FA, Sequist LV, Sandler A, Ross JS, Wang Q, von Roemeling R, Shuster D, Schwartz B. Phase III multinational, randomized, double-blind, placebo-controlled study of tivantinib (ARQ 197) plus erlotinib versus erlotinib alone in previously treated patients with locally advanced or metastatic nonsquamous non-small-cell lung cancer. J Clin Oncol. 2015 Aug 20;33(24):2667-74. Epub 2015 Jul 13. [https://doi.org/10.1200/JCO.2014.60.7317 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/26169611 PubMed] NCT01244191
+##'''Update:''' Goss GD, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Isla D, Morabito A, Min YJ, Ardizzoni A, Bender S, Cseh A, Felip E. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung: Final analysis of the randomised phase 3 LUX-Lung 8 trial. EClinicalMedicine. 2021 Jun 18;37:100940. [https://doi.org/10.1016/j.eclinm.2021.100940 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8225678/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34195574/ PubMed]
-# '''WJOG 5108L:''' Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, Satouchi M, Iwamoto Y, Kanehara M, Fujimoto D, Ikeda N, Murakami H, Daga H, Oguri T, Goto I, Imamura F, Sugawara S, Saka H, Nogami N, Negoro S, Nakagawa K, Nakanishi Y. Randomized phase III study comparing gefitinib with erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016 Sep 20;34(27):3248-57. Epub 2016 Mar 28. [https://doi.org/10.1200/jco.2015.63.4154 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/27022112 PubMed]
+# '''ATTENTION:''' Yoshioka H, Azuma K, Yamamoto N, Takahashi T, Nishio M, Katakami N, Ahn MJ, Hirashima T, Maemondo M, Kim SW, Kurosaki M, Akinaga S, Park K, Tsai CM, Tamura T, Mitsudomi T, Nakagawa K. A randomized, double-blind, placebo-controlled, phase III trial of erlotinib with or without a c-Met inhibitor tivantinib (ARQ 197) in Asian patients with previously treated stage IIIB/IV nonsquamous nonsmall-cell lung cancer harboring wild-type epidermal growth factor receptor (ATTENTION study). Ann Oncol. 2015 Oct;26(10):2066-72. Epub 2015 Jul 7. [https://doi.org/10.1093/annonc/mdv288 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26153496/ PubMed] [https://clinicaltrials.gov/study/NCT01377376 NCT01377376]
-# '''CurrentS:''' Smit EF, Wu YL, Gervais R, Zhou C, Felip E, Feng J, Guclu SZ, Hoiczyk M, Dorokhova E, Freudensprung U, Grange S, Perez-Moreno PD, Mitchell L, Reck M. A randomized, double-blind, phase III study comparing two doses of erlotinib for second-line treatment of current smokers with advanced non-small-cell lung cancer (CurrentS). Lung Cancer. 2016 Sep;99:94-101. Epub 2016 Jun 27. [http://www.lungcancerjournal.info/article/S0169-5002(16)30377-4/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/27565921 PubMed] NCT01183858
+# '''MARQUEE:''' Scagliotti G, von Pawel J, Novello S, Ramlau R, Favaretto A, Barlesi F, Akerley W, Orlov S, Santoro A, Spigel D, Hirsh V, Shepherd FA, Sequist LV, Sandler A, Ross JS, Wang Q, von Roemeling R, Shuster D, Schwartz B. Phase III multinational, randomized, double-blind, placebo-controlled study of tivantinib (ARQ 197) plus erlotinib versus erlotinib alone in previously treated patients with locally advanced or metastatic nonsquamous non-small-cell lung cancer. J Clin Oncol. 2015 Aug 20;33(24):2667-74. Epub 2015 Jul 13. [https://doi.org/10.1200/JCO.2014.60.7317 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26169611/ PubMed] [https://clinicaltrials.gov/study/NCT01244191 NCT01244191]
-# '''IUNO:''' Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. [http://www.lungcancerjournal.info/article/S0169-5002(16)30504-9/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/27987585 PubMed] NCT01328951
+# '''WJOG 5108L:''' Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, Satouchi M, Iwamoto Y, Kanehara M, Fujimoto D, Ikeda N, Murakami H, Daga H, Oguri T, Goto I, Imamura F, Sugawara S, Saka H, Nogami N, Negoro S, Nakagawa K, Nakanishi Y. Randomized phase III study comparing gefitinib with erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016 Sep 20;34(27):3248-57. Epub 2016 Mar 28. [https://doi.org/10.1200/jco.2015.63.4154 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27022112/ PubMed] UMIN000002014
-# '''ECOG-ACRIN 1512:''' Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. Epub 2016 Nov 4. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30561-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154681/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27825638 PubMed] NCT01708954
+# '''CurrentS:''' Smit EF, Wu YL, Gervais R, Zhou C, Felip E, Feng J, Guclu SZ, Hoiczyk M, Dorokhova E, Freudensprung U, Grange S, Perez-Moreno PD, Mitchell L, Reck M. A randomized, double-blind, phase III study comparing two doses of erlotinib for second-line treatment of current smokers with advanced non-small-cell lung cancer (CurrentS). Lung Cancer. 2016 Sep;99:94-101. Epub 2016 Jun 27. [https://doi.org/10.1016/j.lungcan.2016.06.019 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27565921/ PubMed] [https://clinicaltrials.gov/study/NCT01183858 NCT01183858]
-# '''METLung:''' Spigel DR, Edelman MJ, O'Byrne K, Paz-Ares L, Mocci S, Phan S, Shames DS, Smith D, Yu W, Paton VE, Mok T. Results from the phase III randomized trial of onartuzumab plus erlotinib versus erlotinib in previously treated stage IIIB or IV non-small-cell lung cancer: METLung. J Clin Oncol. 2017 Feb;35(4):412-420. Epub 2016 Dec 12. [https://doi.org/10.1200/JCO.2016.69.2160 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/27937096 PubMed] NCT01456325
+# '''IUNO:''' Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. [https://doi.org/10.1016/j.lungcan.2016.10.007 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27987585/ PubMed] [https://clinicaltrials.gov/study/NCT01328951 NCT01328951]
-# Wang Y, Wang H, Jiang Y, Zhang Y, Wang X. A randomized phase III study of combining erlotinib with bevacizumab and panitumumab versus erlotinib alone as second-line therapy for Chinese patients with non-small-cell lung cancer. Biomed Pharmacother. 2017 May;89:875-879. Epub 2017 Mar 6. [https://doi.org/10.1016/j.biopha.2017.02.097 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28282789 PubMed]
+# '''ECOG-ACRIN 1512:''' Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. Epub 2016 Nov 4. [https://doi.org/10.1016/S1470-2045(16)30561-7 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154681/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27825638/ PubMed] [https://clinicaltrials.gov/study/NCT01708954 NCT01708954]
-# '''AvaALL:''' Gridelli C, de Castro Carpeno J, Dingemans AC, Griesinger F, Grossi F, Langer C, Ohe Y, Syrigos K, Thatcher N, Das-Gupta A, Truman M, Donica M, Smoljanovic V, Bennouna J. Safety and Efficacy of Bevacizumab Plus Standard-of-Care Treatment Beyond Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer: The AvaALL Randomized Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):e183486. Epub 2018 Dec 13. Erratum in: JAMA Oncol. 2018 Dec 1;4(12):1792. [https://jamanetwork.com/journals/jamaoncology/article-abstract/2698039 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440713 link to PMC article] '''contains verified protocol in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30177994 PubMed] NCT01351415
+# '''METLung:''' Spigel DR, Edelman MJ, O'Byrne K, Paz-Ares L, Mocci S, Phan S, Shames DS, Smith D, Yu W, Paton VE, Mok T. Results from the phase III randomized trial of onartuzumab plus erlotinib versus erlotinib in previously treated stage IIIB or IV non-small-cell lung cancer: METLung. J Clin Oncol. 2017 Feb;35(4):412-420. Epub 2016 Dec 12. [https://doi.org/10.1200/JCO.2016.69.2160 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27937096/ PubMed] [https://clinicaltrials.gov/study/NCT01456325 NCT01456325]
-# '''JUNIPER:''' Goldman JW, Mazieres J, Barlesi F, Dragnev KH, Koczywas M, Göskel T, Cortot AB, Girard N, Wesseler C, Bischoff H, Nadal E, Park K, Lu S, Taus A, Cobo M, Estrem ST, Wijayawardana SR, Turner K, Oakley GJ 3rd, Hurt KC, Chiang AY, Hossain AM, John WJ, Paz-Ares L. A Randomized Phase III Study of Abemaciclib Versus Erlotinib in Patients with Stage IV Non-small Cell Lung Cancer With a Detectable KRAS Mutation Who Failed Prior Platinum-Based Therapy: JUNIPER. Front Oncol. 2020 Oct 26;10:578756. [https://doi.org/10.3389/fonc.2020.578756 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7649422/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33194700/ PubMed] NCT02152631
+# Wang Y, Wang H, Jiang Y, Zhang Y, Wang X. A randomized phase III study of combining erlotinib with bevacizumab and panitumumab versus erlotinib alone as second-line therapy for Chinese patients with non-small-cell lung cancer. Biomed Pharmacother. 2017 May;89:875-879. Epub 2017 Mar 6. [https://doi.org/10.1016/j.biopha.2017.02.097 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28282789/ PubMed]
+# '''AvaALL:''' Gridelli C, de Castro Carpeno J, Dingemans AC, Griesinger F, Grossi F, Langer C, Ohe Y, Syrigos K, Thatcher N, Das-Gupta A, Truman M, Donica M, Smoljanovic V, Bennouna J. Safety and Efficacy of Bevacizumab Plus Standard-of-Care Treatment Beyond Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer: The AvaALL Randomized Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):e183486. Epub 2018 Dec 13. Erratum in: JAMA Oncol. 2018 Dec 1;4(12):1792. [https://doi.org/10.1001/jamaoncol.2018.3486 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440713 link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30177994/ PubMed] [https://clinicaltrials.gov/study/NCT01351415 NCT01351415]
+# '''JUNIPER:''' Goldman JW, Mazieres J, Barlesi F, Dragnev KH, Koczywas M, Göskel T, Cortot AB, Girard N, Wesseler C, Bischoff H, Nadal E, Park K, Lu S, Taus A, Cobo M, Estrem ST, Wijayawardana SR, Turner K, Oakley GJ 3rd, Hurt KC, Chiang AY, Hossain AM, John WJ, Paz-Ares L. A Randomized Phase III Study of Abemaciclib Versus Erlotinib in Patients with Stage IV Non-small Cell Lung Cancer With a Detectable KRAS Mutation Who Failed Prior Platinum-Based Therapy: JUNIPER. Front Oncol. 2020 Oct 26;10:578756. [https://doi.org/10.3389/fonc.2020.578756 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7649422/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33194700/ PubMed] [https://clinicaltrials.gov/study/NCT02152631 NCT02152631]
+#'''WJOG5108LFS:''' Katakami N, Yokoyama T, Morita S, Okamoto T, Urata Y, Hattori Y, Iwamoto Y, Sato Y, Ikeda N, Takahashi T, Daga H, Oguri T, Fujisaka Y, Nishino K, Sugawara S, Kozuki T, Oki M, Yamamoto N, Nakagawa K. Overall survival analysis of patients enrolled in a randomized phase III trial comparing gefitinib and erlotinib for previously treated advanced lung adenocarcinoma (WJOG5108LFS). Int J Clin Oncol. 2023 Jan;28(1):79-88. Epub 2022 Nov 21. [https://doi.org/10.1007/s10147-022-02266-x link to original article] [https://pubmed.ncbi.nlm.nih.gov/36414827/ PubMed] UMIN000002014
 [[Category:Non-small cell lung cancer regimens]]
 [[Category:Historical regimens]]
 [[Category:Disease-specific pages]]
 [[Category:Lung cancers]]

Difference between revisions of "Non-small cell lung cancer - historical"

Latest revision as of 17:13, 17 July 2024

Neoadjuvant therapy

MIC

Regimen

Chemotherapy

Supportive therapy

Subsequent treatment

References

Adjuvant therapy

Radiation therapy

Regimen

Preceding treatment

Radiotherapy

References

Induction therapy for locally advanced disease

MIC

Regimen

Chemotherapy

Supportive therapy

Subsequent treatment

References

PEV

Regimen

Chemotherapy

Subsequent treatment

References

Definitive therapy for locally advanced disease

MVP & RT

Regimen variant #1

Chemotherapy

Radiotherapy

Regimen variant #2

Chemotherapy

Radiotherapy

References

Maintenance after definitive therapy for inoperable disease

BCG vaccine monotherapy

Regimen

Preceding treatment

Immunotherapy

References

Advanced or metastatic disease, first-line

CAMP

Regimen

Chemotherapy

References

Carboplatin & Cisplatin

Regimen

Chemotherapy

References

CCI

Regimen variant #1

Chemotherapy

Supportive therapy

Regimen variant #2

Chemotherapy

Supportive therapy

References

CISCA

Regimen

Chemotherapy

References

Cisplatin monotherapy

Regimen variant #1, 75 q3wk x 8

Chemotherapy

Regimen variant #2, 100 q3wk

Chemotherapy

Regimen variant #3, 100 q4wk

Chemotherapy

References

Cisplatin & Pemetrexed

Regimen

Chemotherapy

Supportive therapy

References

Cisplatin & Vinblastine

Regimen

Chemotherapy

References

Regimen variant #1, 1000 mg/m², 3 out of 4 weeks

Regimen variant #2, 1250 mg/m², 2 out of 3 weeks

Regimen variant #1, 100 mg/m², 3 out of 4 weeks