Non-small cell lung cancer - historical
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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.
Last updated on 2024-09-06: 34 regimens on this page
52 variants on this page
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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
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
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 | Inconclusive whether non-inferior OS (primary endpoint) 20.5 vs 22 mo (HR not reported) |
2. Carboplatin, Irinotecan, RT | Inconclusive whether non-inferior OS (primary endpoint) 20.5 vs 19.8 mo (HR not reported) |
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
- 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
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
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 on day 1, given 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.
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. Cisplatin; high-dose 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 (Folate) 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 |
2. Irinotecan | Non-inferior OS (primary endpoint) | |||
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 |
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 |
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
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.
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.
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
Ifosfamide monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fossella et al. 2000 (TAX 320) | 1995-1998 | Phase 3 (C) | 1. Docetaxel; 100 mg/m2 | Did not meet primary endpoint of OS |
2. Docetaxel; 75 mg/m2 | Did not meet primary endpoint of 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
- Ifosfamide (Ifex) 2000 mg/m2 IV once per day on days 1 to 3
Supportive therapy
21-day cycles
References
- TAX 320: Fossella FV, DeVore R, Kerr RN, Crawford J, Natale RR, Dunphy F, Kalman L, Miller V, Lee JS, Moore M, Gandara D, Karp D, Vokes E, Kris M, Kim Y, Gamza F, Hammershaimb L; TAX 320 Non-Small Cell Lung Cancer Study Group. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. J Clin Oncol. 2000 Jun;18(12):2354-62. Erratum in: J Clin Oncol. 2004 Jan 1;22(1):209. 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
Irinotecan monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Negoro et al. 2003 | 1995-1998 | Phase 3 (E-de-esc) | 1. Cisplatin & Vindesine | Non-inferior OS (primary endpoint) Median OS: 46 vs 45.6 weeks (HR 0.83, 95% CI 0.64-1.09) |
2. IC | Not reported |
References
- 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
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 OS12 |
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 OS12 |
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 |
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 (primary endpoint) Median OS: 6.8 vs 4.8 mo (HR 0.68, 95% CI 0.49-0.996) |
Regimen variant #3, 225 mg/m2 q3wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lilenbaum et al. 2005 (CALGB 9730) | 1997-2000 | Phase 3 (C) | CP | Did not meet primary endpoint of OS |
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 dosing details in manuscript have been reviewed by our editors 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
- CALGB 9730: Lilenbaum RC, Herndon JE 2nd, List MA, Desch C, Watson DM, Miller AA, Graziano SL, Perry MC, Saville W, Chahinian P, Weeks JC, Holland JC, Green MR. Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the Cancer and Leukemia Group B (study 9730). J Clin Oncol. 2005 Jan 1;23(1):190-6. link to original articledosing details in manuscript have been reviewed by our editors PubMed NCT00003117
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 |
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 |
2. CVb | Inferior OS | |||
Crawford et al. 1996 | 1990-1992 | Randomized (E-RT-switch-ic) | FULV | Seems to have superior OS |
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.
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 |
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
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
Gefitinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gaafar et al. 2011 (EORTC 08021) | 2004-2009 | Phase 3 (E-esc) | Placebo | Did not meet primary endpoint of OS Median OS: 10.9 vs 9.4 mo (HR 0.83, 95% CI 0.60-1.15) |
Zhang et al. 2012 (INFORM) | 2008-09-28 to 2009-08-11 | Phase 3 (E-esc) | Placebo | Superior PFS (primary endpoint) Median PFS: 4.8 vs 2.6 mo (HR 0.42, 95% CI 0.33-0.55) |
Preceding treatment
- First-line platinum-doublet therapy x 4
References
- EORTC 08021: Gaafar RM, Surmont VF, Scagliotti GV, Van Klaveren RJ, Papamichael D, Welch JJ, Hasan B, Torri V, van Meerbeeck JP; EORTC Lung Cancer Group; Italian Lung Cancer Project. A double-blind, randomised, placebo-controlled phase III intergroup study of gefitinib in patients with advanced NSCLC, non-progressing after first line platinum-based chemotherapy (EORTC 08021/ILCP 01/03). Eur J Cancer. 2011 Oct;47(15):2331-40. Epub 2011 Jul 28. link to original article https://doi.org/10.1016/j.ejca.2011.06.045 PubMed NCT00091156
- INFORM: Zhang L, Ma S, Song X, Han B, Cheng Y, Huang C, Yang S, Liu X, Liu Y, Lu S, Wang J, Zhang S, Zhou C, Zhang X, Hayashi N, Wang M; INFORM investigators. Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804): a multicentre, double-blind randomised phase 3 trial. Lancet Oncol. 2012 May;13(5):466-75. Epub 2012 Apr 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00770588
- Update: Zhao H, Fan Y, Ma S, Song X, Han B, Cheng Y, Huang C, Yang S, Liu X, Liu Y, Lu S, Wang J, Zhang S, Zhou C, Wang M, Zhang L; INFORM investigators. Final overall survival results from a phase III, randomized, placebo-controlled, parallel-group study of gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804). J Thorac Oncol. 2015 Apr;10(4):655-64. link to original article PubMed
Sunitinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baggstrom et al. 2017 (CALGB 30607) | 2008-2013 | Phase 3 (E-esc) | Placebo | Superior PFS (primary endpoint) Median PFS: 4.3 vs 2.6 mo (HR 0.62, 95% CI 0.47-0.82) |
Preceding treatment
- CALGB 30607: First-line platinum-doublet therapy x 4, with or without bevacizumab
References
- CALGB 30607: Baggstrom MQ, Socinski MA, Wang XF, Gu L, Stinchcombe TE, Edelman MJ, Baker S Jr, Feliciano J, Novotny P, Hahn O, Crawford JA, Vokes EE. Maintenance sunitinib following initial platinum-based combination chemotherapy in advanced-stage IIIB/IV non-small cell lung cancer: a randomized, double-blind, placebo-controlled phase III study-CALGB 30607 (Alliance). J Thorac Oncol. 2017 May;12(5):843-849. Epub 2017 Feb 1. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00693992
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 Median OS: 9.2 vs 9.3 mo (HR 1.03, 95% CI 0.85-1.25) |
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 (TAILORNSCLC) | 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 (DELTANSCLC) | 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 |
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
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
- 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
- TAILORNSCLC: 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
- DELTANSCLC: 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
- 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
- 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