Difference between revisions of "Small cell lung cancer"
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====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Carboplatin (Paraplatin)]] AUC 5 or 6 IV once on day 1 | + | *[[Carboplatin (Paraplatin)]] AUC 5 or 6 (maximum dose of 1000 mg) IV once on day 1 |
− | **AUC 5 is used if eGFR calculated by EDTA; AUC 6 is used if eGFR calculated by Cockcroft Gault. If eGFR greater than 130 mL/min/1.73m<sup>2</sup>, dose calculation to be capped at GFR = 130 mL/min/1.73m<sup>2</sup> | + | **AUC 5 is used if eGFR calculated by EDTA; AUC 6 is used if eGFR calculated by Cockcroft Gault. If eGFR greater than 130 mL/min/1.73m<sup>2</sup>, dose calculation to be capped at GFR = 130 mL/min/1.73m<sup>2</sup> |
*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
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====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Carboplatin (Paraplatin)]] AUC 5 or 6 IV once on day 1 | + | *[[Carboplatin (Paraplatin)]] AUC 5 or 6 (maximum dose of 1000 mg) IV once on day 1 |
**'''Lee et al. 2009''': AUC 5 is used | **'''Lee et al. 2009''': AUC 5 is used | ||
− | **'''LUNGSTAR''': AUC 5 is used if eGFR calculated by EDTA; AUC 6 is used if eGFR calculated by Cockcroft Gault. If eGFR greater than 130 mL/min/1.73m<sup>2</sup>, dose calculation to be capped at GFR = mL/min/1.73m<sup>2</sup> | + | **'''LUNGSTAR''': AUC 5 is used if eGFR calculated by EDTA; AUC 6 is used if eGFR calculated by Cockcroft Gault. If eGFR greater than 130 mL/min/1.73m<sup>2</sup>, dose calculation to be capped at GFR = mL/min/1.73m<sup>2</sup> |
*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once on day 1, then 100 mg PO BID on days 2 & 3 | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once on day 1, then 100 mg PO BID on days 2 & 3 | ||
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====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Carboplatin (Paraplatin)]] AUC 5 or 6 IV once on day 1 | + | *[[Carboplatin (Paraplatin)]] AUC 5 or 6 (maximum dose of 1000 mg) IV once on day 1 |
**'''Lee et al. 2009''': AUC 5 is used | **'''Lee et al. 2009''': AUC 5 is used | ||
− | **'''LUNGSTAR''': AUC 5 is used if eGFR calculated by EDTA; AUC 6 is used if eGFR calculated by Cockcroft Gault. If eGFR greater than 130 mL/min/1.73m<sup>2</sup>, dose calculation to be capped at GFR = mL/min/1.73m<sup>2</sup> | + | **'''LUNGSTAR''': AUC 5 is used if eGFR calculated by EDTA; AUC 6 is used if eGFR calculated by Cockcroft Gault. If eGFR greater than 130 mL/min/1.73m<sup>2</sup>, dose calculation to be capped at GFR = mL/min/1.73m<sup>2</sup> |
*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2, then 100 mg PO BID on day 3 | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2, then 100 mg PO BID on day 3 | ||
Line 1,913: | Line 1,913: | ||
''von Pawel et al. 1999 does not clearly state the duration of each cycle, but 21 days is used in other CAV regimens, and there was no information in the paper that contradicted this.'' | ''von Pawel et al. 1999 does not clearly state the duration of each cycle, but 21 days is used in other CAV regimens, and there was no information in the paper that contradicted this.'' | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> (maximum dose | + | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> (maximum dose of 2000 mg) (route not specified) once on day 1 |
− | *[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> (maximum dose | + | *[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> (maximum dose of 100 mg) IV once on day 1 |
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1 | *[[Vincristine (Oncovin)]] 2 mg IV once on day 1 | ||
Line 1,938: | Line 1,938: | ||
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1 | ||
− | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose | + | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 |
'''21-day cycle for 4 cycles''' | '''21-day cycle for 4 cycles''' |
Revision as of 03:03, 2 November 2018
Section editor | |
---|---|
Travis Osterman, DO, MS Nashville, TN Twitter: TravisOsterman |
50 regimens on this page
102 variants on this page
|
Guidelines
ASCO
- 2015: Rudin et al. Treatment of small-cell lung cancer: American Society of Clinical Oncology endorsement of the American College of Chest Physicians guideline PubMed
ESMO
- 2013: Früh et al. Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed
NCCN
Limited stage, induction
Carboplatin & Etoposide
back to top |
EP: Etoposide, Paraplatin (Carboplatin)
Variant #1, 2 days of oral etoposide per cycle
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Lee et al. 2009 | Phase III (C) | Carboplatin, Etoposide, Thalidomide, then RT | Seems not superior |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 100 mg PO BID on days 2 & 3
21-day cycle for up to 6 cycles
Subsequent treatment
- Patients with complete or partial responses: Thoracic radiotherapy and prophylactic cranial irradiation, approximately 3 weeks after the last cycle, "according to local practice".
Variant #2, 1 day of oral etoposide per cycle
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Lee et al. 2009 | Phase III (C) | Carboplatin, Etoposide, Thalidomide, then RT | Seems not superior |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 & 2, then 100 mg PO BID on day 3
21-day cycle for up to 6 cycles
Subsequent treatment
- Patients with complete or partial responses: Thoracic radiotherapy and prophylactic cranial irradiation, approximately 3 weeks after the last cycle, "according to local practice".
References
- Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. Epub 2009 Jul 16. link to original article contains verified protocol PubMed
CC/DE & RT
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CC/DE & RT: Cyclophosphamide & Cisplatin alternating with Doxorubicin & Etoposide, with Radiation Therapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Arriagada et al. 1993 | Phase III (E) | Lower-dose CC/DE | Seems to have superior OS |
Here for historic reference.
Chemoradiotherapy
- Cyclophosphamide (Cytoxan)
- Cisplatin (Platinol)
- Doxorubicin (Adriamycin)
- Etoposide (Vepesid)
- External beam radiotherapy
References
- Arriagada R, Le Chevalier T, Pignon JP, Rivière A, Monnet I, Chomy P, Tuchais C, Tarayre M, Ruffié P. Initial chemotherapeutic doses and survival in patients with limited small-cell lung cancer. N Engl J Med. 1993 Dec 16;329(25):1848-52. link to original article PubMed
Cisplatin & Etoposide
back to top |
EP: Etoposide, Platinol (Cisplatin)
Regimen
Study | Evidence |
---|---|
Evans et al. 1985 | Phase II |
Patients with limited stage disease responding to therapy received prophylactic cranial irradiation, 4 Gy fractions given once per day x 5 fractions (total dose: 20 Gy) over 5 days between cycles 3 and 4.
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV slow push once per day on days 1 to 3, given second
- Etoposide (Vepesid) 100 mg/m2 IV over at least 30 minutes once per day on days 1 to 3, given first
Supportive medications
- Dexamethasone (Decadron) 10 mg IV once prior to chemotherapy
- Metoclopramide (Reglan) 10 mg IV/PO once prior to chemotherapy
- Prochlorperazine (Compazine) 10 mg PO/IM once prior to chemotherapy
- "No special efforts were made to hydrate the patients," though PO fluid intake was encouraged, and 500 mL normal saline was given with etoposide infusion.
21 to 28-day cycle for 6 cycles
Subsequent treatment
References
- Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. link to original article contains verified protocol PubMed
Limited stage, definitive chemoradiotherapy
Carboplatin, Etoposide, RT
back to top |
EP & RT: Etoposide, Paraplatin (Carboplatin), Radiation Therapy
Variant #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Skarlos et al. 2001 | Randomized Phase II (E) | Carboplatin, Etoposide, early HTRT | Might have superior ORR |
Chemoradiotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 60 minutes once on day 1, given first, before etoposide
- Etoposide (Vepesid) 100 mg/m2 IV over 2 hours once per day on days 1 to 3, given second, after carboplatin
- Concurrent hyperfractionated thoracic radiation therapy (HTRT), 1.5 Gy fractions given twice per day (at least 4, but preferably 6 hours between fractions) x 30 fractions (total dose: 45 Gy) over 3 weeks. Skarlos et al. 2001 examined two different timings for radiation therapy. There was no significant difference between early vs. late HTRT, though there was a trend toward higher response rate for late HTRT. Early HTRT is given during cycle 1 of chemotherapy; late HTRT is given during cycle 4 of chemotherapy.
21-day cycle for up to 6 cycles
Subsequent treatment
- Patients with CR: Prophylactic cranial irradiation
Variant #2
Study | Evidence |
---|---|
Okamoto et al. 1999 | Phase II |
Patients in Okamoto et al. 1999 were greater than or equal to 70 years old.
Chemoradiotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1, 'given first
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 3, given second
- Thoracic radiation, given third
- Palliative radiation therapy was allowed to control persistent pain from bony metastases
Supportive medications
- Dexamethasone (Decadron) 8 mg IV once per day on days 1 to 3 prior to chemotherapy
- Granisetron 40 mcg/kg IV once per day on days 1 to 3 prior to chemotherapy
- G-CSF 2 mcg/kg SC given for grade 3 or greater leukopenia/neutropenia
28-day cycle for up to 4 cycles
References
- Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I, Masutani M, Nakata K, Tsuchiya S, Isobe H, Saijo N. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999 Nov;17(11):3540-5. link to original article contains verified protocol PubMed
- Skarlos DV, Samantas E, Briassoulis E, Panoussaki E, Pavlidis N, Kalofonos HP, Kardamakis D, Tsiakopoulos E, Kosmidis P, Tsavdaridis D, Tzitzikas J, Tsekeris P, Kouvatseas G, Zamboglou N, Fountzilas G. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol. 2001 Sep;12(9):1231-8. link to original article contains verified protocol PubMed
CEV & RT
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CEV & RT: Cyclophosphamide, Epirubicin, Vincristine, Radiation Therapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sundstrøm et al. 2002 | Phase III (C) | Cisplatin, Etoposide, RT | Inferior OS |
Inferior to EP & RT; placed here for reference reasons only.
Chemoradiotherapy
Subsequent treatment
- Patients with CR: Prophylactic cranial irradiation
References
- Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. link to original article contains verified protocol PubMed
Cisplatin, Etoposide, RT
back to top |
EP & RT: Etoposide, Platinol (Cisplatin), Radiation Therapy
Variant #1, 60/360
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Turrisi et al. 1999 (Intergroup 0096) | Phase III (E) | Cisplatin, Etoposide, once per day RT | Seems to have superior OS |
Chemoradiotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
- Concurrent radiation therapy, 1.50 Gy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 45 Gy)
21-day cycle for 4 cycles
Subsequent treatment
- After completing 4 cycles of chemotherapy, patients were restaged. Because of the high rate of brain metastases (50%), patients with CR were offered Prophylactic cranial irradiation
Variant #2, 70/300, early RT
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Sun et al. 2013 | Phase III (C) | EP & late RT | Seems not superior | Seems to have higher rates of neutropenic fever |
Chemoradiotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Concurrent radiation therapy, 2.10 Gy fractions x 25 fractions over 5 weeks, given during cycle 1 of chemotherapy (total dose: 52.5 Gy)
21-day cycle for 4 cycles
Variant #3, 70/300, late RT
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Sun et al. 2013 | Phase III (E) | EP & early RT | Seems not superior | Seems to have lower rates of neutropenic fever |
Chemoradiotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Concurrent radiation therapy, 2.10 Gy fractions x 25 fractions over 5 weeks, given during cycle 3 of chemotherapy (total dose: 52.5 Gy)
21-day cycle for 4 cycles
Variant #4, 75 with partially oral etoposide
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sundstrøm et al. 2002 | Phase III (E) | CEV & RT | Superior OS |
Chemoradiotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once on day 1; then 200 mg/m2 PO once per day on days 2 to 4, taken on an empty stomach
- Concurrent thoracic radiation therapy, 2.8 Gy fractions given once per day x 15 fractions (total dose: 42 Gy) over 3 weeks, given "between the third and fourth chemotherapy courses"
Supportive medications
- "Standard prehydration and posthydration procedures were followed in conjunction with cisplatin administration."
21-day cycle for up to 5 cycles
Subsequent treatment
- Patients with CR: Prophylactic cranial irradiation
Variant #5, 75/300
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Faivre-Finn et al. 2017 (CONVERT) | Phase III (E) | Cisplatin, Etoposide, once per day RT | Seems not superior |
Chemoradiotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Concurrent radiation therapy, 1.50 Gy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 45 Gy)
21-day cycle for 4 or 6 cycles
Variant #6, 75/300, split doses of cisplatin
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Faivre-Finn et al. 2017 (CONVERT) | Phase III (E) | Cisplatin, Etoposide, once per day RT | Seems not superior |
Chemoradiotherapy
- Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1 to 3
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Concurrent radiation therapy, 1.50 Gy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 45 Gy)
21-day cycle for 4 or 6 cycles
Variant #7, 80/300 x 1
Study | Evidence |
---|---|
Saito et al. 2006 (WJTOG 9902) | Phase II |
Chemoradiotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Concurrent thoracic radiation therapy, 1.5 Gy fractions given twice per day (at least 4, but preferably 6 hours between fractions) x 30 fractions (total dose: 45 Gy) over 3 weeks, started on cycle 1 day 2 of chemotherapy
28-day cycle for 1 cycle
Subsequent treatment
Variant #8, 80/300 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Takada et al. 2002 (JCOG 9104) | Phase III (E) | Cisplatin, Etoposide, sequential RT | Might have superior OS |
Chemoradiotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Concurrent thoracic radiation therapy, 1.5 Gy fractions given twice per day (4 or more hours between fractions) x 30 fractions (total dose: 45 Gy) over 3 weeks, started on cycle 1 day 2 of chemotherapy
28-day cycle for 4 cycles
Subsequent treatment
- Patients with CR or near-CR ("a scar-like shadow on chest films but no positive cytology and/or bronchoscopic biopsy"): Prophylactic cranial irradiation
References
- Intergroup 0096: Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999 Jan 28;340(4):265-71. link to original article contains verified protocol PubMed
- JCOG 9104: Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, Nishiwaki Y, Watanabe K, Noda K, Tamura T, Fukuda H, Saijo N. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002 Jul 15;20(14):3054-60. link to original article contains verified protocol PubMed content property of HemOnc.org
- Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. link to original article contains verified protocol PubMed
- Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, Ando M, Tada T, Fukuoka M; West Japan Thoracic Oncology Group 9902. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006 Nov 20;24(33):5247-52. link to original article contains verified protocol PubMed
- Sun JM, Ahn YC, Choi EK, Ahn MJ, Ahn JS, Lee SH, Lee DH, Pyo H, Song SY, Jung SH, Jo JS, Jo J, Sohn HJ, Suh C, Lee JS, Kim SW, Park K. Phase III trial of concurrent thoracic radiotherapy with either first- or third-cycle chemotherapy for limited-disease small-cell lung cancer. Ann Oncol. 2013 Aug;24(8):2088-92. Epub 2013 Apr 16. Erratum in: Ann Oncol. 2014 Aug;25(8):1672. link to original article contains verified protocol PubMed
- CONVERT: Faivre-Finn C, Snee M, Ashcroft L, Appel W, Barlesi F, Bhatnagar A, Bezjak A, Cardenal F, Fournel P, Harden S, Le Pechoux C, McMenemin R, Mohammed N, O'Brien M, Pantarotto J, Surmont V, Van Meerbeeck JP, Woll PJ, Lorigan P, Blackhall F; CONVERT Study Team. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017 Aug;18(8):1116-1125. Epub 2017 Jun 20. link to PMC article contains verified protocol PubMed
Limited state, consolidation after upfront therapy
Cisplatin & Irinotecan
back to top |
IP: Irinotecan, Platinol (Cisplatin)
Regimen
Study | Evidence |
---|---|
Saito et al. 2006 (WJTOG 9902) | Phase II |
Preceding treatment
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Irinotecan (Camptosar) 60 mg/m2 IV once per day on days 1, 8, 15
Supportive medications
- G-CSF (no additional details given) starting after day 4
28-day cycle for 3 cycles
Subsequent treatment
- Patients with complete or good partial responses: Prophylactic cranial irradiation
References
- WJTOG 9902: Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, Ando M, Tada T, Fukuoka M; West Japan Thoracic Oncology Group 9902. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006 Nov 20;24(33):5247-52. link to original article contains verified protocol PubMed
Radiation therapy
back to top |
Regimen
Study | Evidence |
---|---|
Evans et al. 1985 | Phase II |
Preceding treatment
- EP x 6
Radiotherapy
- "Patients who did not have evidence of tumor spread beyond the mediastinum and/or ipsilateral supraclavicular notes" received thoracic radiation in 250 cGy fractions x 10 fractions (total dose: 25 Gy)
References
- Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. link to original article contains verified protocol PubMed
- Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. Epub 2009 Jul 16. link to original article does not contain protocol PubMed
Whole brain irradiation
back to top |
PCI: Prophylactic Cranial Irradiation
Variant #1, 20 Gy
Study | Evidence |
---|---|
Cox et al. 1981 | Non-randomized |
Evans et al. 1985 | Phase II |
Skarlos et al. 2001 | Non-randomized portion of RCT |
Note: in Evans et al. 1985, the WB-XRT is given in-between cycles 3 & 4.
Preceding treatment
- Evans et al. 1985: EP x 3
- Skarlos et al. 2001: EP & early HTRT versus EP & late HTRT
Radiotherapy
- Whole brain irradiation, 4 Gy fractions given once per day x 5 fractions (total dose: 20 Gy)
Subsequent treatment
- Evans et al. 1985: EP x 3
Variant #2, 24 Gy
Study | Evidence |
---|---|
Takada et al. 2002 (JCOG 9104) | Non-randomized portion of RCT |
Preceding treatment
- EP & RT versus EP, then RT
Prophylactic whole-brain irradiation
- Whole brain irradiation, 1.5 Gy fractions given twice per day, 5 days per week, x 16 fractions (total dose: 24 Gy)
Variant #3, 25 Gy
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Turrisi et al. 1999 (Intergroup 0096) | Non-randomized portion of RCT | ||
Saito et al. 2006 (WJTOG 9902) | Phase II | ||
Le Péchoux et al. 2009 (PCI 99-01/EORTC 22003-08004/RTOG 0212/IFCT 99-01) | Phase III (C) | PCI x 36 Gy | Seems not superior |
Preceding treatment
- Intergroup 0096: EP & once-daily RT versus EP & twice-daily RT
- WJTOG 9902: EP & RT, then IP x 3
Radiotherapy
- Whole brain irradiation, 2.5 Gy fractions x 10 fractions (total dose: 25 Gy)
Variant #4, 30 Gy
Study | Evidence |
---|---|
Sundstrøm et al. 2002 | Non-randomized portion of RCT |
Preceding treatment
Radiotherapy
- Whole brain irradiation, 2 Gy fractions given once per day x 15 fractions (total dose: 30 Gy)
References
- Cox JD, Stanley K, Petrovich Z, Paig C, Yesner R. Cranial irradiation in cancer of the lung of all cell types. JAMA. 1981 Feb 6;245(5):469-72. link to original article PubMed
- Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. link to original article contains verified protocol PubMed
- Intergroup 0096: Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999 Jan 28;340(4):265-71. link to original article contains verified protocol PubMed
- Meta-analysis: Aupérin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens RJ, Kristjansen PE, Johnson BE, Ueoka H, Wagner H, Aisner J; Prophylactic Cranial Irradiation Overview Collaborative Group. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 1999 Aug 12;341(7):476-84. link to original article PubMed
- JCOG 9104: Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, Nishiwaki Y, Watanabe K, Noda K, Tamura T, Fukuda H, Saijo N. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002 Jul 15;20(14):3054-60. link to original article contains verified protocol PubMed content property of HemOnc.org
- Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. link to original article contains verified protocol PubMed
- WJTOG 9902: Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, Ando M, Tada T, Fukuoka M; West Japan Thoracic Oncology Group 9902. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006 Nov 20;24(33):5247-52. link to original article contains verified protocol PubMed
- PCI 99-01/EORTC 22003-08004/RTOG 0212/IFCT 99-01: Le Péchoux C, Dunant A, Senan S, Wolfson A, Quoix E, Faivre-Finn C, Ciuleanu T, Arriagada R, Jones R, Wanders R, Lerouge D, Laplanche A; Prophylactic Cranial Irradiation (PCI) Collaborative Group. Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomised clinical trial. Lancet Oncol. 2009 May;10(5):467-74. Epub 2009 Apr 20. link to original article PubMed
Extensive stage, induction
ACE
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ACE: Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide
AVE: Adriamycin (Doxorubicin), Vepesid (Etoposide), Endoxan (Cyclophosphamide)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Klastersky et al. 1985 | Phase II | ORR: 66% | |
Sculier et al. 1993 | Phase III (C) | Multi-drug regimen | Seems not superior |
Baka et al. 2008 | Phase III (C) | EP | Seems not superior |
Used as a comparator arm in older studies; here for reference purposes only. The non-randomized results of Klastersky et al. 1985 established this regimen as a standard control.
Chemotherapy
References
- Klastersky J, Sculier JP, Dumont JP, Becquart D, Vandermoten G, Rocmans P, Michel J, Longeval E, Dalesio O. Combination chemotherapy with adriamycin, etoposide, and cyclophosphamide for small cell carcinoma of the lung: a study by the EORTC Lung Cancer Working Party (Belgium). Cancer. 1985 Jul 1;56(1):71-5. link to original article PubMed
- Sculier JP, Paesmans M, Bureau G, Dabouis G, Libert P, Vandermoten G, Van Cutsem O, Berchier MC, Ries F, Michel J, Sergysels R, Mommen P, Klastersky J. Multiple-drug weekly chemotherapy versus standard combination regimen in small-cell lung cancer: a phase III randomized study conducted by the European Lung Cancer Working Party. J Clin Oncol. 1993 Oct;11(10):1858-65. link to original article PubMed
- Baka S, Califano R, Ferraldeschi R, Aschroft L, Thatcher N, Taylor P, Faivre-Finn C, Blackhall F, Lorigan P. Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer. Br J Cancer. 2008 Aug 5;99(3):442-7. link to original article link to PMC article contains protocol PubMed
Belotecan & Cisplatin
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BP: Belotecan and Platinol (Cisplatin)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Oh et al. 2016 (COMBAT) | Phase III (E) | EP 60/100 | Non-inferior RR |
Note: the total number of planned cycles is not described in the manuscript; total duration information here was provided by the authors.
Chemotherapy
- Belotecan (Camptobell) 0.5 mg/m2 IV over 30 minutes once per day on days 1 to 4
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
21-day cycle for 4 to 8 cycles
References
- COMBAT: Oh IJ, Kim KS, Park CK, Kim YC, Lee KH, Jeong JH, Kim SY, Lee JE, Shin KC, Jang TW, Lee HK, Lee KY, Lee SY. Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: a multi-center randomized phase III trial. BMC Cancer. 2016 Aug 26;16:690. link to original article link to original article contains verified protocol PubMed
Carboplatin & Etoposide
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EP: Etoposide and Paraplatin (Carboplatin)
CE: Carboplatin and Etoposide
Ca/E: Carboplatin and Etoposide
Variant #1, AUC 5/80
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sekine et al. 2013 | Phase III (C) | Amrubicin | Seems not superior |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 3
21-day cycle for 4 to 6 cycles
Variant #2, AUC 5/100
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Socinski et al. 2009 | Phase III (C) | Carboplatin & Pemetrexed | Superior OS |
Spigel et al. 2011 (SALUTE) | Randomized Phase II (C) | Carboplatin, Etoposide, Bevacizumab | Seems to have inferior PFS |
Ready et al. 2015 (CALGB 30504) | Non-randomized portion of RCT | ||
Jalal et al. 2017 (MATISSE) | Randomized Phase II (C) | PaCE | Might have superior OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Supportive medications
- Socinksi et al. 2009: "supportive therapies, such as erythropoietic agents or granulocyte colony-stimulating factors, were administered according to the American Society of Clinical Oncology guidelines"
21-day cycle for 4 to 6 cycles
Subsequent treatment
- CALGB 30504, SD or better: Observation versus sunitinib maintenance
Variant #3, AUC 5 or 6/120
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Seckl et al. 2017 (LUNGSTAR) | Phase III (C) | Carboplatin, Etoposide, Pravastatin | Seems not superior |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 or 6 (maximum dose of 1000 mg) IV once on day 1
- AUC 5 is used if eGFR calculated by EDTA; AUC 6 is used if eGFR calculated by Cockcroft Gault. If eGFR greater than 130 mL/min/1.73m2, dose calculation to be capped at GFR = 130 mL/min/1.73m2
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
21-day cycle for 6 cycles
Variant #4, AUC 5 or 6/120, 2 days of oral etoposide per cycle
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Lee et al. 2009 | Phase III (C) | Carboplatin, Etoposide, Thalidomide | Seems not superior |
Seckl et al. 2017 (LUNGSTAR) | Phase III (C) | Carboplatin, Etoposide, Pravastatin | Seems not superior |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 or 6 (maximum dose of 1000 mg) IV once on day 1
- Lee et al. 2009: AUC 5 is used
- LUNGSTAR: AUC 5 is used if eGFR calculated by EDTA; AUC 6 is used if eGFR calculated by Cockcroft Gault. If eGFR greater than 130 mL/min/1.73m2, dose calculation to be capped at GFR = mL/min/1.73m2
- Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 100 mg PO BID on days 2 & 3
21-day cycle for up to 6 cycles
Variant #5, AUC 5 or 6/120, 1 day of oral etoposide per cycle
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Lee et al. 2009 | Phase III (C) | Carboplatin, Etoposide, Thalidomide | Seems not superior |
Seckl et al. 2017 (LUNGSTAR) | Phase III (C) | Carboplatin, Etoposide, Pravastatin | Seems not superior |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 or 6 (maximum dose of 1000 mg) IV once on day 1
- Lee et al. 2009: AUC 5 is used
- LUNGSTAR: AUC 5 is used if eGFR calculated by EDTA; AUC 6 is used if eGFR calculated by Cockcroft Gault. If eGFR greater than 130 mL/min/1.73m2, dose calculation to be capped at GFR = mL/min/1.73m2
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 & 2, then 100 mg PO BID on day 3
21-day cycle for up to 6 cycles
Variant #6, AUC 5/140
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Schmittel et al. 2006 | Randomized Phase II (E) | IP | Might have inferior OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 in 500 mL 5% glucose solution IV over 60 minutes once on day 1
- Etoposide (Vepesid) 140 mg/m2 in 1000 mL normal saline IV over 90 minutes once per day on days 1 to 3
Supportive medications
- 5-HT3 antagonist IV before chemotherapy
- Loperamide (Imodium) 4 mg PO prn first episode of diarrhea, then loperamide 2 mg PO Q2H until diarrhea stops
21-day cycle for up to 6 cycles
Variant #7, AUC 5/100, 28-day cycles
Study | Evidence |
---|---|
Okamoto et al. 1999 | Phase II |
Quoix et al. 2001 | Phase II |
Patients in Okamoto et al. 1999 and Quoix et al. 2001 were greater than or equal to 70 years old.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1, given first
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 3, given second
- Palliative radiation therapy was allowed to control persistent pain from bony metastases
Supportive medications
- Dexamethasone (Decadron) 8 mg IV once on days 1 to 3 prior to chemotherapy
- Granisetron 40 mcg/kg IV once on days 1 to 3 prior to chemotherapy
- Okamoto et al. 1999: G-CSF 2 mcg/kg SC given for grade 3 or greater leukopenia/neutropenia
- Quiox et al. 2001: "Haematopoietic growth factors were allowed as prophylactic or curative treatment only if grade 4 neutropenia greater than 7 days occurred"
28-day cycle for 4 to 6 cycles
References
- Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I, Masutani M, Nakata K, Tsuchiya S, Isobe H, Saijo N. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999 Nov;17(11):3540-5. link to original article contains verified protocol PubMed
- Quoix E, Breton JL, Daniel C, Jacoulet P, Debieuvre D, Paillot N, Kessler R, Moreau L, Coëtmeur D, Lemarié E, Milleron B. Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: a phase II study. Ann Oncol. 2001 Jul;12(7):957-62. link to original article contains verified protocol PubMed
- Schmittel A, Fischer von Weikersthal L, Sebastian M, Martus P, Schulze K, Hortig P, Reeb M, Thiel E, Keilholz U. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006 Apr;17(4):663-7. Epub 2006 Jan 19. link to original article contains verified protocol PubMed
- Update: Schmittel A, Sebastian M, Fischer von Weikersthal L, Martus P, Gauler TC, Kaufmann C, Hortig P, Fischer JR, Link H, Binder D, Fischer B, Caca K, Eberhardt WE, Keilholz U; Arbeitsgemeinschaft Internistische Onkologie Thoracic Oncology Study Group. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011 Aug;22(8):1798-804. Epub 2011 Jan 25. link to original article contains verified protocol PubMed
- Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. Epub 2009 Jul 16. link to original article contains verified protocol PubMed
- Socinski MA, Smit EF, Lorigan P, Konduri K, Reck M, Szczesna A, Blakely J, Serwatowski P, Karaseva NA, Ciuleanu T, Jassem J, Dediu M, Hong S, Visseren-Grul C, Hanauske AR, Obasaju CK, Guba SC, Thatcher N. Phase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer. J Clin Oncol. 2009 Oct 1;27(28):4787-92. Epub 2009 Aug 31. link to original article contains verified protocol PubMed
- SALUTE: Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. link to original article contains verified protocol PubMed
- Sekine I, Okamoto H, Horai T, Nakagawa K, Ohmatsu H, Yokoyama A, Katakami N, Shibuya M, Saijo N, Fukuoka M. A randomized phase III study of single-agent amrubicin vs carboplatin/etoposide in elderly patients with extensive-disease small-cell lung cancer. Clin Lung Cancer. 2014 Mar;15(2):96-102. Epub 2013 Nov 14. link to original article contains protocol PubMed
- CALGB 30504: Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. link to original article link to PMC article contains verified protocol PubMed
- LUNGSTAR: Seckl MJ, Ottensmeier CH, Cullen M, Schmid P, Ngai Y, Muthukumar D, Thompson J, Harden S, Middleton G, Fife KM, Crosse B, Taylor P, Nash S, Hackshaw A. Multicenter, phase III, randomized, double-blind, placebo-controlled trial of pravastatin added to first-line standard chemotherapy in small-cell lung cancer (LUNGSTAR). J Clin Oncol. 2017 May 10;35(14):1506-1514. Epub 2017 Feb 27. link to original article contains verified protocol link to PMC article PubMed
- MATISSE: Jalal SI, Lavin P, Lo G, Lebel F, Einhorn L. Carboplatin and etoposide with or without palifosfamide in untreated extensive-stage small-cell lung cancer: A multicenter, adaptive, randomized phase III study (MATISSE). J Clin Oncol. 2017 Aug 10;35(23):2619-2623. Epub 2017 Jun 12. link to original article contains verified protocol PubMed
Carboplatin, Etoposide, Bevacizumab
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Spigel et al. 2011 (SALUTE) | Randomized Phase II (E) | Carboplatin & Etoposide | Seems to have superior PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
References
- Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. link to original article contains verified protocol PubMed
Carboplatin & Irinotecan
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IP: Irinotecan, Paraplatin (Carboplatin)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Schmittel et al. 2006 | Randomized Phase II (E) | EP | Might have superior OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 in 500 mL 5% glucose solution IV over 60 minutes once on day 1
- Irinotecan (Camptosar) 50 mg/m2 in 250 mL normal saline IV over 30 minutes once per day on days 1, 8, 15
Supportive medications
- 5-HT3 antagonist IV before chemotherapy
- Loperamide (Imodium) 4 mg PO prn first episode of diarrhea, then 2 mg PO Q2H until diarrhea stops
28-day cycle for up to 6 cycles
References
- Schmittel A, Fischer von Weikersthal L, Sebastian M, Martus P, Schulze K, Hortig P, Reeb M, Thiel E, Keilholz U. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006 Apr;17(4):663-7. Epub 2006 Jan 19. link to original article contains verified protocol PubMed
- Update: Schmittel A, Sebastian M, Fischer von Weikersthal L, Martus P, Gauler TC, Kaufmann C, Hortig P, Fischer JR, Link H, Binder D, Fischer B, Caca K, Eberhardt WE, Keilholz U; Arbeitsgemeinschaft Internistische Onkologie Thoracic Oncology Study Group. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011 Aug;22(8):1798-804. Epub 2011 Jan 25. link to original article contains verified protocol PubMed
Carboplatin, Paclitaxel, Ipilimumab
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Variant #1, phased ipilimumab
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Reck et al. 2011 | Randomized Phase II (E) | 1. Carboplatin & Paclitaxel | Seems to have superior irPFS |
2. Carboplatin, Paclitaxel, concurrent Ipilimumab | Not reported |
Chemoimmunotherapy
- Carboplatin (Paraplatin) AUC 6 IV once per day on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once per day on day 1
- Ipilimumab (Yervoy) as follows:
- Cycles 1 & 2: no treatment
- Cycles 3 to 6: 10 mg/kg IV once per day on day 1
21-day cycle for up to 6 cycles
Subsequent treatment
Variant #2, concurrent ipilimumab
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Reck et al. 2011 | Randomized Phase II (E) | 1. Carboplatin & Paclitaxel | Seems not superior |
2. Carboplatin, Paclitaxel, phased Ipilimumab | Not reported |
Chemoimmunotherapy
- Carboplatin (Paraplatin) AUC 6 IV once per day on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once per day on day 1
- Ipilimumab (Yervoy) as follows:
- Cycles 1 to 4: 10 mg/kg IV once per day on day 1
- Cycles 5 & 6: no treatment
21-day cycle for up to 6 cycles
Subsequent treatment
References
- Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013 Jan;24(1):75-83. link to original article contains verified protocol PubMed
CAV
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CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine
Variant #1, flat-dose vincristine
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Evans et al. 1987 | Phase III (C) | CAV/PE | Seems to have inferior OS | Similar toxicity |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
21-day cycle 6 cycles
Variant #2, uncapped vincristine
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Girling 1996 | Phase III (C) | Oral Etoposide | Seems to have superior OS | |
Ettinger et al. 2002 (ECOG E1588) | Phase III (C) | 1. Ifosfamide | Seems not superior | More toxic |
2. Teniposide | Seems not superior | More toxic |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
21-day cycle for 4 to 6 cycles
Subsequent treatment
- ECOG E1588, CR: 2 more cycles of CAV, then PCI
- ECOG E1588, PR: CAV until progression of disease, then salvage EP
References
- Evans WK, Feld R, Murray N, Willan A, Coy P, Osoba D, Shepherd FA, Clark DA, Levitt M, MacDonald A, Wilson K, Shelley W, Pater J. Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: a multicenter, randomized clinical trial by the National Cancer Institute of Canada. Ann Intern Med. 1987 Oct;107(4):451-8. Erratum in: Ann Intern Med 1988 Mar;108(3):496. link to original article contains protocol PubMed
- Girling DJ; Medical Research Council Lung Cancer Working Party. Comparison of oral etoposide and standard intravenous multidrug chemotherapy for small-cell lung cancer: a stopped multicentre randomised trial. Lancet. 1996 Aug 31;348(9027):563-6. link to original article PubMed
- ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; Eastern Cooperative Oncology Group. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. link to original article contains verified protocol PubMed
CDE
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CDE: Cyclophosphamide, Doxorubicin, Etoposide
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Postmus et al. 1996 | Phase III (C) | CDE/VIMP | Seems not superior |
Note: this regimen is here for historical purposes, only.
Chemotherapy
References
- Postmus PE, Scagliotti G, Groen HJ, Gozzelino F, Burghouts JT, Curran D, Sahmoud T, Kirkpatrick A, Giaccone G, Splinter TA. Standard versus alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: an EORTC phase III trial. Eur J Cancer. 1996 Aug;32A(9):1498-503. link to original article PubMed
CEV
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CEV: Cyclophosphamide, Epirubicin, Vincristine
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sundstrøm et al. 2002 | Phase III (C) | Cisplatin & Etoposide | Seems not superior |
Not commonly used; here for reference purposes only.
Chemotherapy
References
- Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. link to original article contains verified protocol PubMed
Cisplatin & Etoposide
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EP: Etoposide and Platinol (Cisplatin)
PE: Platinol (Cisplatin) and Etoposide
Variant #1, 60/100
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Oh et al. 2016 (COMBAT) | Phase III (C) | BP | Non-inferior RR |
Note: the total number of planned cycles is not described in the manuscript; total duration information here was provided by the authors.
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for 4 to 8 cycles
Variant #2, 60/120
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hanna et al. 2006 | Phase III (C) | Cisplatin & Irinotecan | Seems not superior |
Seckl et al. 2017 (LUNGSTAR) | Phase III (C) | Cisplatin, Etoposide, Pravastatin | Seems not superior |
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
Supportive medications
- Per Hanna et al. 2006:
- G-CSF used according to 1999 American Society of Clinical Oncology guidelines
- "Erythropoietin was allowed at the discretion of the treating physician."
21-day cycle for 4 to 6 cycles
Variant #3, 60/120, 1 day of oral etoposide per cycle
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Seckl et al. 2017 (LUNGSTAR) | Phase III (C) | Cisplatin, Etoposide, Pravastatin | Seems not superior |
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 & 2, then 100 mg PO BID on day 3
21-day cycle for up to 6 cycles
Variant #4, 60/120, 2 days of oral etoposide per cycle
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Seckl et al. 2017 (LUNGSTAR) | Phase III (C) | Cisplatin, Etoposide, Pravastatin | Seems not superior |
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 100 mg PO BID on days 2 & 3
21-day cycle for up to 6 cycles
Variant #5, 75/100
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Spigel et al. 2011 (SALUTE) | Randomized Phase II (C) | Cisplatin, Etoposide, Bevacizumab | Seems to have inferior PFS |
Fink et al. 2012 | Phase III (C) | Cisplatin & Topotecan | Non-inferior OS |
Etoposide & Topotecan | Not reported |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for 4 (SALUTE) or 6 (Fink et al. 2012) cycles
Variant #6, 75/100, 3 days of oral etoposide per cycle
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sundstrøm et al. 2002 | Phase III (E) | CEV | Seems not superior |
Note: Patients in Sundstrøm et al. 2002 with extensive stage disease did not routinely receive radiation therapy. "However, chest or cranial irradiation was optional if severe symptoms could not be palliated by chemotherapy."
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once on day 1, then 200 mg/m2 PO once per day on days 2 to 4, taken on an empty stomach
Supportive medications
- "Standard prehydration and posthydration procedures were followed in conjunction with cisplatin administration."
21-day cycle for up to 5 cycles
Variant #7, 75/100, cisplatin split over 3 days
Study | Evidence |
---|---|
Evans et al. 1985 | Phase II |
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV slow push once per day on days 1 to 3, given second
- Etoposide (Vepesid) 100 mg/m2 IV over at least 30 minutes once per day on days 1 to 3, given first
- Patients with disease responding to therapy received prophylactic cranial irradiation, 4 Gy fractions given daily x 5 fractions (total dose: 20 Gy) over 5 days between cycles 3 and 4
- Locoregional radiation therapy was only used if symptoms persisted after 6 cycles of treatment: Radiation therapy, 250 cGy/rad fractions x 10 fractions (total dose: 2500 cGy/rad), given after cycle 6 of chemotherapy
Supportive medications
- Dexamethasone (Decadron) 10 mg IV once prior to chemotherapy
- Metoclopramide (Reglan) 10 mg IV/PO once prior to chemotherapy
- Prochlorperazine (Compazine) 10 mg PO/IM once prior to chemotherapy
- "No special efforts were made to hydrate the patients," though PO fluid intake was encouraged, and 500 mL normal saline was given with etoposide infusion.
21 to 28-day cycle for 6 cycles
Variant #8, 80/80
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ihde et al. 1994 | Phase III (C) | High-dose EP | Seems not superior |
Niell et al. 2005 (CALGB 9732) | Phase III (C) | PET | Seems not superior |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 3
- Concurrent radiation therapy with the start of chemotherapy was given to patients with brain metastases, epidural metastases, and impending pathologic bone fractures
- Patients with carcinomatous meningitis received Methotrexate (MTX) IT (dose/schedule not specified) and radiation to functionally compromised areas of the CNS
Supportive medications
- "Half-normal saline was infused for 2 to 6 hours with Cisplatin (Platinol), usually in conjunction with a diuretic."
- Corticosteroids were usually given for patients receiving radiation therapy for brain and epidural metastases.
21-day cycle for 4 to 8 cycles
Subsequent treatment
- Ihde et al. 1994, CR after 4 cycles: an additional 4 cycles. Some patients were randomized to receive prophylactic cranial irradiation. Radiation could also be given at the patient's request. No details about dose/schedule given.
- Ihde et al. 1994, PR, no response, or progressive disease: Salvage CAV or "an individualized 3-drug in vitro-selected regimen (IVSR) during cycles 5 to 8 if drug-sensitivity testing data were available."
Variant #9, 80/100
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Fukuoka et al. 1991 | Phase III (C) | 1. CAV | Not reported |
2. CAV/PE | Might have inferior OS | ||
Noda et al. 2002 (JCOG 9511) | Phase III (C) | IP | Inferior OS |
Eckardt et al. 2006 | Phase III (C) | Cisplatin & Topotecan | Non-inferior OS |
Lara et al. 2009 (SWOG S0124) | Phase III (C) | IP | Seems not superior |
Zatloukal et al. 2010 | Phase III (C) | IP | Non-inferior OS |
Ready et al. 2015 (CALGB 30504) | Non-randomized portion of RCT | ||
Sun et al. 2016 | Phase III (C) | Amrubicin & Cisplatin | Might have inferior OS |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Fukuoka et al. 1991 gave etoposide on days 1, 3, 5
Supportive medications
- "Hydration and administration of antiemetic drugs."
21-day cycle for 4 to 6 cycles
Subsequent treatment
- CALGB 30504, SD or better: Observation versus sunitinib maintenance
Variant #10, 80/100, cisplatin split over 4 days
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Loehrer et al. 1995 | Phase III (C) | VIP | Seems to have inferior OS |
Chemotherapy
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 4
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 4
21-day cycle for 4 cycles
Variant #11, 80/120, 2 days of oral etoposide per cycle
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Baka et al. 2008 | Phase III (E) | ACE | Seems not superior |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 240 mg/m2/day PO on days 2 & 3
21-day cycle for 6 cycles
Variant #12, 100/400
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Roth et al. 1992 | Phase III (C) | 1. CAV 2. CAV/PE |
Seems not superior |
Chemotherapy
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 5
- Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 5
21-day cycle for 4 cycles
References
- Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. link to original article contains verified protocol PubMed
- Fukuoka M, Furuse K, Saijo N, Nishiwaki Y, Ikegami H, Tamura T, Shimoyama M, Suemasu K. Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer. J Natl Cancer Inst. 1991 Jun 19;83(12):855-61. link to original article contains protocol PubMed
- Roth BJ, Johnson DH, Einhorn LH, Schacter LP, Cherng NC, Cohen HJ, Crawford J, Randolph JA, Goodlow JL, Broun GO, Omura GA, Greco FA. Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1992 Feb;10(2):282-91. link to original article contains verified protocol PubMed
- Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, Edison M, Phelps RM, Lesar M, Phares JC, Grayson J, Minna JD, Johnson BE. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol. 1994 Oct;12(10):2022-34. link to original article contains verified protocol PubMed
- Loehrer PJ Sr, Ansari R, Gonin R, Monaco F, Fisher W, Sandler A, Einhorn LH. Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study. J Clin Oncol. 1995 Oct;13(10):2594-9. link to original article contains verified protocol PubMed
- JCOG 9511: Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N; Japan Clinical Oncology Group. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):85-91. link to original article contains verified protocol PubMed
- Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. link to original article contains verified protocol PubMed
- Niell HB, Herndon JE 2nd, Miller AA, Watson DM, Sandler AB, Kelly K, Marks RS, Perry MC, Ansari RH, Otterson G, Ellerton J, Vokes EE, Green MR; Cancer and Leukemia Group. Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colony-stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732. J Clin Oncol. 2005 Jun 1;23(16):3752-9. link to original article contains verified protocol PubMed
- Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2038-43. link to original article contains verified protocol PubMed
- Eckardt JR, von Pawel J, Papai Z, Tomova A, Tzekova V, Crofts TE, Brannon S, Wissel P, Ross G. Open-label, multicenter, randomized, phase III study comparing oral topotecan/cisplatin versus etoposide/cisplatin as treatment for chemotherapy-naive patients with extensive-disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2044-51. link to original article contains protocol PubMed
- Baka S, Califano R, Ferraldeschi R, Aschroft L, Thatcher N, Taylor P, Faivre-Finn C, Blackhall F, Lorigan P. Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer. Br J Cancer. 2008 Aug 5;99(3):442-7. link to original article link to PMC article contains protocol PubMed
- SWOG S0124: Lara PN Jr, Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, Jett J, Langer CJ, Kuebler JP, Dakhil SR, Chansky K, Gandara DR. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol. 2009 May 20;27(15):2530-5. Epub 2009 Apr 6. link to original article link to PMC article contains protocol PubMed
- Zatloukal P, Cardenal F, Szczesna A, Gorbunova V, Moiseyenko V, Zhang X, Cisar L, Soria JC, Domine M, Thomas M. A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease. Ann Oncol. 2010 Sep;21(9):1810-6. Epub 2010 Mar 15. link to original article contains protocol PubMed
- SALUTE: Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. link to original article contains verified protocol PubMed
- Fink TH, Huber RM, Heigener DF, Eschbach C, Waller C, Steinhauer EU, Virchow JC, Eberhardt F, Schweisfurth H, Schroeder M, Ittel T, Hummler S, Banik N, Bogenrieder T, Acker T, Wolf M; “Aktion Bronchialkarzinom” (ABC Study Group). Topotecan/cisplatin compared with cisplatin/etoposide as first-line treatment for patients with extensive disease small-cell lung cancer: final results of a randomized phase III trial. J Thorac Oncol. 2012 Sep;7(9):1432-9. link to original article contains protocol PubMed
- CALGB 30504: Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. link to original article link to PMC article contains verified protocol PubMed
- Sun Y, Cheng Y, Hao X, Wang J, Hu C, Han B, Liu X, Zhang L, Wan H, Xia Z, Liu Y, Li W, Hou M, Zhang H, Xiu Q, Zhu Y, Feng J, Qin S, Luo X. Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer. BMC Cancer. 2016 Apr 9;16:265. link to original article link to PMC article contains verified protocol PubMed
- COMBAT: Oh IJ, Kim KS, Park CK, Kim YC, Lee KH, Jeong JH, Kim SY, Lee JE, Shin KC, Jang TW, Lee HK, Lee KY, Lee SY. Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: a multi-center randomized phase III trial. BMC Cancer. 2016 Aug 26;16:690. link to original article link to original article contains verified protocol PubMed
- LUNGSTAR: Seckl MJ, Ottensmeier CH, Cullen M, Schmid P, Ngai Y, Muthukumar D, Thompson J, Harden S, Middleton G, Fife KM, Crosse B, Taylor P, Nash S, Hackshaw A. Multicenter, phase III, randomized, double-blind, placebo-controlled trial of pravastatin added to first-line standard chemotherapy in small-cell lung cancer (LUNGSTAR). J Clin Oncol. 2017 May 10;35(14):1506-1514. Epub 2017 Feb 27. link to original article contains verified protocol link to PMC article PubMed
Cisplatin, Etoposide, Bevacizumab
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Spigel et al. 2011 (SALUTE) | Randomized Phase II (E) | Cisplatin & Etoposide | Seems to have superior PFS |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
References
- SALUTE: Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. link to original article contains verified protocol PubMed
Cisplatin & Irinotecan
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IP: Irinotecan, Platinol (Cisplatin)
Variant #1, 30/65
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hanna et al. 2006 | Phase III (E) | Cisplatin & Etoposide | Seems not superior |
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1 & 8
- Irinotecan (Camptosar) 65 mg/m2 IV once per day on days 1 & 8
Supportive medications
- G-CSF used according to 1999 American Society of Clinical Oncology guidelines
- "Erythropoietin was allowed at the discretion of the treating physician."
21-day cycle for 4 cycles; additional cycles could be given at physician discretion
Variant #2, 60/60
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Noda et al. 2002 (JCOG 9511) | Phase III (E) | EP | Superior OS |
Lara et al. 2009 (SWOG S0124) | Phase III (E) | EP | Seems not superior |
Satouchi et al. 2014 (JCOG 0509) | Phase III (C) | Amrubicin & Cisplatin | Superior OS |
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Irinotecan (Camptosar) 60 mg/m2 IV once per day on days 1, 8, 15
Supportive medications
- "Hydration and administration of antiemetic drugs."
28-day cycle for 4 cycles
Variant #3, 80/65
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Zatloukal et al. 2010 | Phase III (E) | EP | Non-inferior OS |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Irinotecan (Camptosar) 65 mg/m2 IV once per day on days 1 & 8
21-day cycle for 6 cycles
References
- JCOG 9511: Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N; Japan Clinical Oncology Group. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):85-91. link to original article contains verified protocol PubMed
- Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2038-43. link to original article contains verified protocol PubMed
- SWOG S0124: Lara PN Jr, Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, Jett J, Langer CJ, Kuebler JP, Dakhil SR, Chansky K, Gandara DR. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol. 2009 May 20;27(15):2530-5. Epub 2009 Apr 6. link to original article link to PMC article contains protocol PubMed
- Zatloukal P, Cardenal F, Szczesna A, Gorbunova V, Moiseyenko V, Zhang X, Cisar L, Soria JC, Domine M, Thomas M. A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease. Ann Oncol. 2010 Sep;21(9):1810-6. Epub 2010 Mar 15. link to original article contains protocol PubMed
- JCOG 0509: Satouchi M, Kotani Y, Shibata T, Ando M, Nakagawa K, Yamamoto N, Ichinose Y, Ohe Y, Nishio M, Hida T, Takeda K, Kimura T, Minato K, Yokoyama A, Atagi S, Fukuda H, Tamura T, Saijo N. Phase III study comparing amrubicin plus cisplatin with irinotecan plus cisplatin in the treatment of extensive-disease small-cell lung cancer: JCOG 0509. J Clin Oncol. 2014 Apr 20;32(12):1262-8. Epub 2014 Mar 17. link to original article contains verified protocol PubMed
Docetaxel monotherapy
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Regimen
Study | Evidence |
---|---|
Hesketh et al. 1999 | Phase II |
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
21-day cycles
References
- Hesketh PJ, Crowley JJ, Burris HA 3rd, Williamson SK, Balcerzak SP, Peereboom D, Goodwin JW, Gross HM, Moore DF Jr, Livingston RB, Gandara DR. Evaluation of docetaxel in previously untreated extensive-stage small cell lung cancer: a Southwest Oncology Group phase II trial. Cancer J Sci Am. 1999 Jul-Aug;5(4):237-41. contains protocol PubMed
Ifosfamide monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Ettinger et al. 2002 (ECOG E1588) | Phase III (E) | 1. CAV | Seems not superior | Less toxic |
2. Teniposide | Seems not superior | Not reported |
Chemotherapy
- Ifosfamide (Ifex) 1500 mg/m2 IV once per day on days 1 to 5
Supportive medications
- Mesna (Mesnex) 300 mg/m2 (route not specified) given three times per day on days 1 to 5; 0, 4, and 8 hours after each dose of ifosfamide
21-day cycle for 4 to 6 cycles
Subsequent treatment
- Patients with CR: another 2 cycles of ifosfamide, then prophylactic whole-brain irradiation if still in CR
- Patients with PR: ifosfamide until progression of disease, then salvage EP
References
- ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; Eastern Cooperative Oncology Group. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. link to original article contains verified protocol PubMed
Teniposide monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Ettinger et al. 2002 (ECOG E1588) | Phase III (E) | 1. CAV | Seems not superior | Less toxic |
2. Ifosfamide | Seems not superior | Not reported |
Chemotherapy
- Teniposide (Vumon) 60 mg/m2 IV once per day on days 1 to 5
21-day cycle for 4 to 6 cycles
Subsequent treatment
- Patients with CR received another 2 cycles of teniposide. Patients with PR received teniposide until progression of disease, upon which they then received salvage EP therapy. Patients with complete response after 6 to 8 cycles of teniposide received prophylactic whole-brain irradiation:
Prophylactic whole-brain irradiation
Radiation starts 1 week after completion of induction chemotherapy.
- External beam radiotherapy, 2.5 Gy fractions x 10 fractions (total dose: 25 Gy)
References
- Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; Eastern Cooperative Oncology Group. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. link to original article contains verified protocol PubMed
VIP
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VIP: Vepesid (Etoposide), Ifosfamide, Platinol (Cisplatin)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Loehrer et al. 1995 | Phase III (E) | Cisplatin & Etoposide | Seems to have superior OS |
This is of historic interest; due to excess toxicity and the difficult administration schedule, it is not commonly used.
Chemotherapy
- Etoposide (Vepesid) 75 mg/m2 IV once per day on days 1 to 4
- Ifosfamide (Ifex) 1200 mg/m2 IV once per day on days 1 to 4
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 4
21-day cycle for 4 cycles
References
- Loehrer PJ Sr, Ansari R, Gonin R, Monaco F, Fisher W, Sandler A, Einhorn LH. Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study. J Clin Oncol. 1995 Oct;13(10):2594-9. link to original article contains verified protocol PubMed
Extensive stage, consolidation after first-line therapy
Whole brain irradiation
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PCI: Prophylactic Cranial Irradiation
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ettinger et al. 2002 (ECOG E1588) | Non-randomized portion of RCT | ||
Slotman et al. 2007 (EORTC 22993) | Phase III (E) | Observation | Superior OS |
Preceding treatment
- ECOG E1588: CAV versus Ifosfamide versus Teniposide
- EORTC 22993: Chemotherapy x 4 to 6 cycles (regimen not specified)
Radiotherapy
- Whole brain irradiation by one of the following: 20 Gy in 5 or 8 fractions, 24 Gy in 12 fractions, 25 Gy in 10 fractions, or 30 Gy in 10 or 12 fractions
One course
References
- Meta-analysis: Aupérin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens RJ, Kristjansen PE, Johnson BE, Ueoka H, Wagner H, Aisner J; Prophylactic Cranial Irradiation Overview Collaborative Group. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 1999 Aug 12;341(7):476-84. link to original article PubMed
- ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; Eastern Cooperative Oncology Group. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. link to original article contains verified protocol PubMed
- EORTC 22993: Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, Postmus P, Collette L, Musat E, Senan S; EORTC Radiation Oncology Group and Lung Cancer Group. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007 Aug 16;357(7):664-72. link to original article contains protocol PubMed
Extensive stage, maintenance after first-line therapy
Bevacizumab monotherapy
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Regimen
Study | Evidence |
---|---|
Spigel et al. 2011 (SALUTE) | Non-randomized portion of RCT |
Preceding treatment
- Carboplatin, Etoposide, Bevacizumab induction x 4 or Cisplatin, Etoposide, Bevacizumab induction x 4
Chemotherapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. link to original article contains verified protocol PubMed
Ipilimumab monotherapy
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Regimen
Study | Evidence |
---|---|
Reck et al. 2011 | Non-randomized portion of RCT |
Preceding treatment
Immunotherapy
- Ipilimumab (Yervoy) 10 mg/kg IV once per day on day 1
12-week cycles
References
- Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013 Jan;24(1):75-83. link to original article contains verified protocol PubMed
Observation
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ready et al. 2015 (CALGB 30504) | Randomized Phase II (C) | Sunitinib monotherapy | Seems to have inferior PFS |
No further treatment.
Preceding treatment
- Carboplatin & Etoposide or Cisplatin & Etoposide for 4 to 6 cycles
References
- CALGB 30504: Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. link to original article link to PMC article contains verified protocol PubMed
Sunitinib monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ready et al. 2015 (CALGB 30504) | Randomized Phase II (E) | Observation | Seems to have superior PFS |
Preceding treatment
- Carboplatin & Etoposide or Cisplatin & Etoposide for 4 to 6 cycles
Chemotherapy
- Sunitinib (Sutent) 150 mg PO once on day 1, then 37.5 mg PO once per day
Continued indefinitely
References
- CALGB 30504: Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. link to original article link to PMC article contains verified protocol PubMed
Relapsed or refractory disease
Amrubicin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Pawel et al. 2014 (ACT-1) | Phase III (E) | Topotecan | Seems to have superior PFS |
Chemotherapy
- Amrubicin (Calsed) 40 mg/m2 IV over 5 minutes once per day on days 1 to 3
Supportive medications
- "Prophylactic antibiotics were recommended for patients at high risk of infectious complications."
21-day cycle for 6 cycles or until progression of disease
Patients who had at least stable disease by cycle 6 could receive another 6 cycles of treatment.
References
- von Pawel J, Jotte R, Spigel DR, O'Brien ME, Socinski MA, Mezger J, Steins M, Bosquée L, Bubis J, Nackaerts K, Trigo JM, Clingan P, Schütte W, Lorigan P, Reck M, Domine M, Shepherd FA, Li S, Renschler MF. Randomized Phase III Trial of Amrubicin Versus Topotecan As Second-Line Treatment for Patients With Small-Cell Lung Cancer. J Clin Oncol. 2014 Dec 10;32(35):4012-9. Epub 2014 Nov 10. link to original article contains verified protocol PubMed
Bendamustine monotherapy
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Regimen
Study | Evidence | Efficacy |
---|---|---|
Lammers et al. 2014 | Phase II | 33% (95% CI, 14-52%) |
Chemotherapy
- Bendamustine 120 mg/m2 IV once per day on days 1 & 2
21-day cycle for up to 6 cycles
References
- Lammers PE, Shyr Y, Li CI, Hutchison AS, Sandler A, Carbone DP, Johnson DH, Keedy VL, Horn L. Phase II study of bendamustine in relapsed chemotherapy sensitive or resistant small-cell lung cancer. J Thorac Oncol. 2014 Apr;9(4):559-62. link to PMC article contains verified protocol PubMed
Best supportive care
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
O'Brien et al. 2006 | Phase III (C) | Oral topotecan | Seems to have inferior OS |
No active antineoplastic treatment.
References
- O'Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cuceviá B, Juhasz G, Thatcher N, Ross GA, Dane GC, Crofts T. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006 Dec 1;24(34):5441-7. link to original article contains verified protocol PubMed
CAV
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CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine
Variant #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Pawel et al. 1999 | Phase III (C) | Topotecan | Seems not superior |
von Pawel et al. 1999 does not clearly state the duration of each cycle, but 21 days is used in other CAV regimens, and there was no information in the paper that contradicted this.
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 (maximum dose of 2000 mg) (route not specified) once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 (maximum dose of 100 mg) IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
Supportive medications
- G-CSF use per physician discretion
21-day cycles, given until progression of disease, unacceptable toxicity, or 6 cycles beyond maximal response
Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion.
Variant #2
Study | Evidence |
---|---|
Ihde et al. 1994 | Non-randomized portion of RCT |
Treatment given after progression on standard-dose EP versus high-dose EP. Ihde et al. 1994 did not specifically say that the three medications were all given on day 1, but this is assumed to be the case based on other CAV regimens.
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
21-day cycle for 4 cycles
References
- Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, Edison M, Phelps RM, Lesar M, Phares JC, Grayson J, Minna JD, Johnson BE. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol. 1994 Oct;12(10):2022-34. link to original article contains verified protocol PubMed
- von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. link to original article contains verified protocol PubMed
CDE
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CDE: Cyclophosphamide, Doxorubicin, Etoposide
Regimen
Study | Evidence |
---|---|
Postmus et al. 1987 | Phase II |
Note: this regimen is here for historical purposes, only.
Chemotherapy
References
- Postmus PE, Berendsen HH, van Zandwijk N, Splinter TA, Burghouts JT, Bakker W. Retreatment with the induction regimen in small cell lung cancer relapsing after an initial response to short term chemotherapy. Eur J Cancer Clin Oncol. 1987 Sep;23(9):1409-11. PubMed
Cisplatin & Etoposide
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EP: Etoposide, Platinol (Cisplatin)
Variant #1
Study | Evidence |
---|---|
Ettinger et al. 2002 (ECOG E1588) | Non-randomized portion of RCT |
Treatment given after progression on CAV versus ifosfamide versus teniposide.
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
21-day cycles
References
- Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; Eastern Cooperative Oncology Group. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. link to original article contains verified protocol PubMed
Cisplatin, Etoposide, Irinotecan
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Goto et al. 2016 (JCOG0605) | Phase III (E) | Topotecan | Superior OS |
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1 & 8
- Etoposide (Vepesid) 60 mg/m2 IV once per day on days 1 to 3
- Irinotecan (Camptosar) 90 mg/m2 IV once on day 8
Supportive medications
- G-CSF SC once per day beginning on cycle 1 day 9, continued throughout except for days of chemotherapy
14-day cycle for 5 cycles
References
- Goto K, Ohe Y, Shibata T, Seto T, Takahashi T, Nakagawa K, Tanaka H, Takeda K, Nishio M, Mori K, Satouchi M, Hida T, Yoshimura N, Kozuki T, Imamura F, Kiura K, Okamoto H, Sawa T, Tamura T; JCOG0605 investigators. Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as second-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1147-57. Epub 2016 Jun 14. link to original article contains protocol PubMed
Docetaxel monotherapy
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Regimen
Study | Evidence |
---|---|
Smyth et al. 1994 | Phase II |
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
21-day cycles
References
- Smyth JF, Smith IE, Sessa C, Schoffski P, Wanders J, Franklin H, Kaye SB; The Early Clinical Trials Group of the EORTC. Activity of docetaxel (Taxotere) in small cell lung cancer. Eur J Cancer. 1994;30A(8):1058-60. link to SD article contains protocol PubMed
Etoposide monotherapy
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Regimen
Study | Evidence |
---|---|
Einhorn et al. 1990 | Phase II |
Johnson et al. 1990 | Phase II |
Chemotherapy
- Etoposide (Vepesid) 50 mg/m2 PO once per day, taken every morning on an empty stomach
Supportive medications
- No routine antiemetics used.
21-day cycles
References
- Einhorn LH, Pennington K, McClean J. Phase II trial of daily oral VP-16 in refractory small cell lung cancer: a Hoosier Oncology Group study. Semin Oncol. 1990 Feb;17(1 Suppl 2):32-5. Not available online; abstract contains protocol PubMed
- Johnson DH, Greco FA, Strupp J, Hande KR, Hainsworth JD. Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin Oncol. 1990 Oct;8(10):1613-7. link to original article contains verified protocol PubMed
Epirubicin & Ifosfamide
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EI: Epirubicin, Ifosfamide
Regimen
Study | Evidence |
---|---|
Jacot et al. 2012 | Phase II |
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Ifosfamide (Ifex) 3000 mg/m2 IV once per day on days 1 & 2
Supportive medications
- Mesna (Mesnex) (dose/route/schedule not specified) on days 1 & 2
- G-CSF use per physician discretion
28-day cycle for up to 6 cycles, until progression of disease, or unacceptable toxicity
References
- Jacot W, Pujol JL, Chakra M, Molinier O, Bozonnat MC, Gervais R, Quantin X. Epirubicin and ifosfamide in relapsed or refractory small cell lung cancer patients. Lung Cancer. 2012 Feb;75(2):213-6. Epub 2011 Aug 9. link to original article contains verified protocol PubMed
Gemcitabine monotherapy
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Regimen
Study | Evidence |
---|---|
van der Lee et al. 2001 | Phase II |
Masters et al. 2003 (ECOG 1597) | Phase II |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 in 250 mL normal saline IV over 30 minutes once per day on days 1, 8, 15
- Patients in Masters et al. 2003 with less than grade 2 toxicity with cycle 1 received 1250 mg/m2 IV over 30 minutes once per day on days 1, 8, 15 of cycles 2 and on
28-day cycle for up to 5 cycles; varies depending on reference. Masters et al. 2003 did not specify a maximum number of cycles.
References
- van der Lee I, Smit EF, van Putten JW, Groen HJ, Schlösser NJ, Postmus PE, Schramel FM. Single-agent gemcitabine in patients with resistant small-cell lung cancer. Ann Oncol. 2001 Apr;12(4):557-61. link to original article contains verified protocol PubMed
- Masters GA, Declerck L, Blanke C, Sandler A, DeVore R, Miller K, Johnson D; Eastern Cooperative Oncology Group. Phase II trial of gemcitabine in refractory or relapsed small-cell lung cancer: Eastern Cooperative Oncology Group Trial 1597. J Clin Oncol. 2003 Apr 15;21(8):1550-5. link to original article contains verified protocol PubMed
Ifosfamide monotherapy
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Regimen
Study | Evidence |
---|---|
Cantwell et al. 1988 | Phase II |
Chemotherapy
- Ifosfamide (Ifex) 5000 mg/m2 IV once on day 1
Supportive medications
- Mesna (Mesnex) 5000 mg/m2 IV once on day 1
21-day cycles
References
- Cantwell BM, Bozzino JM, Corris P, Harris AL. The multidrug resistant phenotype in clinical practice; evaluation of cross resistance to ifosfamide and mesna after VP16-213, doxorubicin and vincristine (VPAV) for small cell lung cancer. Eur J Cancer Clin Oncol. 1988 Feb;24(2):123-9. link to SD article contains protocol PubMed
- Review: Marangolo M, Giovanis P. Ifosfamide in small cell lung cancer. Oncology. 2003;65 Suppl 2:46-9. Review. link to original article PubMed
Ifosfamide & Paclitaxel
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PI: Paclitaxel, Ifosfamide
Regimen
Study | Evidence |
---|---|
Park et al. 2007 | Phase II |
Chemotherapy
- Ifosfamide (Ifex) 2500 mg/m2 IV over 2 hours once per day on days 1 & 2
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Supportive medications
- Mesna (Mesnex) 500 mg/m2 IV given three times per day on days 1 & 2: 15 minutes before, 4 hours after, and 8 hours after ifosfamide (total dose: 1500 mg/m2/day)
21-day cycles
References
- Park S, Ahn MJ, Ahn JS, Lee J, Hong YS, Park BB, Lee SC, Hwang IG, Park JO, Lim H, Kang WK, Park K. Combination chemotherapy with paclitaxel and ifosfamide as the third-line regimen in patients with heavily pretreated small cell lung cancer. Lung Cancer. 2007 Oct;58(1):116-22. Epub 2007 Jul 12. link to original article contains verified protocol PubMed
Ipilimumab & Nivolumab
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Variant #1
Study | Evidence |
---|---|
Antonia et al. 2016 (CheckMate 032) | Phase I/II |
Note: it is unclear which schedule of ipilimumab & nivolumab is preferred based on the abstract.
Immunotherapy
- Ipilimumab (Yervoy) 1 mg/kg IV once on day 1
- Nivolumab (Opdivo) 3 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
Variant #2
Study | Evidence |
---|---|
Antonia et al. 2016 (CheckMate 032) | Phase I/II |
Note: it is unclear which schedule of ipilimumab & nivolumab is preferred based on the abstract.
Immunotherapy
- Ipilimumab (Yervoy) 3 mg/kg IV once on day 1
- Nivolumab (Opdivo) 1 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
References
- CheckMate 032: Antonia SJ, López-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, Jäger D, Pietanza MC, Le DT, de Braud F, Morse MA, Ascierto PA, Horn L, Amin A, Pillai RN, Evans J, Chau I, Bono P, Atmaca A, Sharma P, Harbison CT, Lin CS, Christensen O, Calvo E. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883-95. Epub 2016 Jun 4. link to original article contains protocol PubMed
Irinotecan monotherapy
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Regimen
Study | Evidence |
---|---|
Masuda et al. 1992 | Phase II, <20 pts |
Chemotherapy
- Irinotecan (Camptosar) 100 mg/m2 in 500 mL normal saline IV over 90 minutes once per week
Supportive medications
- No routine prophylaxis against diarrhea, nausea, or vomiting used.
References
- Masuda N, Fukuoka M, Kusunoki Y, Matsui K, Takifuji N, Kudoh S, Negoro S, Nishioka M, Nakagawa K, Takada M. CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol. 1992 Aug;10(8):1225-9. link to original article contains verified protocol PubMed
Nivolumab monotherapy
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Regimen
Study | Evidence |
---|---|
Antonia et al. 2016 (CheckMate 032) | Phase I/II |
Immunotherapy
- Nivolumab (Opdivo) 3 mg/kg IV once on day 1
14-day cycles until progression or intolerance
References
- Antonia SJ, López-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, Jäger D, Pietanza MC, Le DT, de Braud F, Morse MA, Ascierto PA, Horn L, Amin A, Pillai RN, Evans J, Chau I, Bono P, Atmaca A, Sharma P, Harbison CT, Lin CS, Christensen O, Calvo E. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883-95. Epub 2016 Jun 4. link to original article contains protocol PubMed
Paclitaxel monotherapy
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Variant #1, every 3 weeks
Study | Evidence |
---|---|
Smit et al. 1998 | Phase II |
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 in 250 to 1000 mL of D5 or normal saline IV over 3 hours once on day 1
Supportive medications
- Dexamethasone (Decadron) 8 mg PO given twice, 12 and 6 hours prior to paclitaxel
- Clemastine (Tavist) 2 mg IV push once 30 minutes prior to paclitaxel
- One of the following H2 blockers:
- Cimetidine (Tagamet) 300 mg IV push once 30 minutes prior to paclitaxel
- Ranitidine (Zantac) 50 mg IV push once 30 minutes prior to paclitaxel
21-day cycle for up to 5 cycles, progression of disease, or unacceptable toxicity
Variant #2, weekly paclitaxel
Study | Evidence |
---|---|
Yamamoto et al. 2006 | Phase II |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36
Supportive medications
- Dexamethasone (Decadron) 20 mg IV once 30 minutes prior to paclitaxel
- Ranitidine (Zantac) 50 mg IV once 30 minutes prior to paclitaxel
- Diphenhydramine (Benadryl) 50 mg IV once 30 minutes prior to paclitaxel
- If ANC less than 1000/uL or WBC count less than 2 x 109/L, G-CSF 2 mcg/kg SC once per day is given until WBC count greater than or equal to 10 x 109/L, except on days that paclitaxel is given
8-week cycles
References
- Smit EF, Fokkema E, Biesma B, Groen HJ, Snoek W, Postmus PE. A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer. Br J Cancer. 1998;77(2):347-51. contains verified protocol link to PMC article PubMed
- Yamamoto N, Tsurutani J, Yoshimura N, Asai G, Moriyama A, Nakagawa K, Kudoh S, Takada M, Minato Y, Fukuoka M. Phase II study of weekly paclitaxel for relapsed and refractory small cell lung cancer. Anticancer Res. 2006 Jan-Feb;26(1B):777-81. link to original article contains verified protocol PubMed
Temozolomide monotherapy
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Variant #1
Study | Evidence |
---|---|
Zauderer et al. 2014 | Phase II |
Chemotherapy
- Temozolomide (Temodar) 200 mg/m2 PO once per day on days 1 to 5
Supportive medications
- Ondansetron (Zofran) 8 mg PO once 30 minutes prior to each dose
28-day cycles
Variant #2
Study | Evidence |
---|---|
Pietanza et al. 2012 | Phase II |
Chemotherapy
- Temozolomide (Temodar) 75 mg/m2 PO once per day on days 1 to 21, with no food 2 hours before or 1 hour after temozolomide
Supportive medications
- Ondansetron (Zofran) 8 mg PO once prior to temozolomide prn nausea
- Patients with at least grade 3 lymphopenia received prophylaxis for Pneumocystis carinii pneumonia (no specific medication/dose/schedule listed)
28-day cycles
References
- Pietanza MC, Kadota K, Huberman K, Sima CS, Fiore JJ, Sumner DK, Travis WD, Heguy A, Ginsberg MS, Holodny AI, Chan TA, Rizvi NA, Azzoli CG, Riely GJ, Kris MG, Krug LM. Phase II trial of temozolomide in patients with relapsed sensitive or refractory small cell lung cancer, with assessment of methylguanine-DNA methyltransferase as a potential biomarker. Clin Cancer Res. 2012 Feb 15;18(4):1138-45. Epub 2012 Jan 6. link to original article contains verified protocol PubMed
- Zauderer MG, Drilon A, Kadota K, Huberman K, Sima CS, Bergagnini I, Sumner DK, Travis WD, Heguy A, Ginsberg MS, Holodny AI, Riely GJ, Kris MG, Krug LM, Pietanza MC. Trial of a 5-day dosing regimen of temozolomide in patients with relapsed small cell lung cancers with assessment of methylguanine-DNA methyltransferase. Lung Cancer. 2014 Nov;86(2):237-40. Epub 2014 Aug 17. contains verified protocol link to PMC article PubMed
Topotecan monotherapy
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Variant #1, 1.0 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Goto et al. 2016 (JCOG0605) | Phase III (C) | Cisplatin, Etoposide, Irinotecan | Inferior OS |
Chemotherapy
- Topotecan (Hycamtin) 1.0 mg/m2 IV over 30 minutes once per day on days 1 to 5
21-day cycle for 4 cycles
Variant #2, 1.5 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Pawel et al. 1999 | Phase III (E) | CAV | Seems not superior |
Eckardt et al. 2007 | Phase III (C) | Oral topotecan | Seems not superior |
von Pawel et al. 2014 (ACT-1) | Phase III (C) | Amrubicin | Seems to have inferior PFS |
Chemotherapy
- Topotecan (Hycamtin) 1.5 mg/m2 IV over 30 minutes once per day on days 1 to 5
Supportive medications
- (varies depending on reference):
- G-CSF use per physician discretion
- In von Pawel et al. 2014 (ACT-1), "Prophylactic antibiotics were recommended for patients at high risk of infectious complications."
21-day cycles
Duration varies depending on reference:
- In von Pawel et al. 1999 treatment is given until progression of disease, unacceptable toxicity, or 6 cycles beyond maximal response. Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion.
- In Eckardt et al. 2007, patients with complete or partial response continued treatment progression of disease or 2 cycles beyond best response. Patients with stable disease received at least 4 cycles therapy.
- In von Pawel et al. 2014 (ACT-1), treatment was given for 6 cycles or until progression of disease. Patients who had at least stable disease by cycle 6 could receive another 6 cycles of treatment.
Variant #3, oral route
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
O'Brien et al. 2006 | Phase III (E) | Best supportive care | Seems to have superior OS |
Eckardt et al. 2007 | Phase III (E) | IV topotecan (1.5 mg/m2) | Seems not superior |
Chemotherapy
- Topotecan (Hycamtin) 2.3 mg/m2 PO once per day on days 1 to 5
21-day cycles
Duration of treatment details vary depending on reference. In O'Brien et al. 2006, treatment is given for at least 4 cycles, though this depended on tolerability and response. In Eckardt et al. 2007, patients with complete or partial response continued treatment progression of disease or 2 cycles beyond best response. Patients with stable disease received at least 4 cycles of therapy.
References
- von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. link to original article contains verified protocol PubMed
- O'Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cuceviá B, Juhasz G, Thatcher N, Ross GA, Dane GC, Crofts T. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006 Dec 1;24(34):5441-7. link to original article contains verified protocol PubMed
- Eckardt JR, von Pawel J, Pujol JL, Papai Z, Quoix E, Ardizzoni A, Poulin R, Preston AJ, Dane G, Ross G. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol. 2007 May 20;25(15):2086-92. link to original article contains verified protocol PubMed
- von Pawel J, Jotte R, Spigel DR, O'Brien ME, Socinski MA, Mezger J, Steins M, Bosquée L, Bubis J, Nackaerts K, Trigo JM, Clingan P, Schütte W, Lorigan P, Reck M, Domine M, Shepherd FA, Li S, Renschler MF. Randomized Phase III Trial of Amrubicin Versus Topotecan As Second-Line Treatment for Patients With Small-Cell Lung Cancer. J Clin Oncol. 2014 Dec 10;32(35):4012-9. Epub 2014 Nov 10. link to original article contains verified protocol PubMed
- Goto K, Ohe Y, Shibata T, Seto T, Takahashi T, Nakagawa K, Tanaka H, Takeda K, Nishio M, Mori K, Satouchi M, Hida T, Yoshimura N, Kozuki T, Imamura F, Kiura K, Okamoto H, Sawa T, Tamura T; JCOG0605 investigators. Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as second-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1147-57. Epub 2016 Jun 14. link to original article contains protocol PubMed
Vinorelbine monotherapy
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Variant #1, 25 mg/m2
Study | Evidence |
---|---|
Furuse et al. 1996 | Phase II |
Chemotherapy
- Vinorelbine (Navelbine) 25 mg/m2 IV once per week
Continued indefinitely
Variant #2, 30 mg/m2
Study | Evidence |
---|---|
Jassem et al. 1993 | Phase II |
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once per week
Continued indefinitely
References
- Jassem J, Karnicka-Mlodkowska H, van Pottelsberghe C, van Glabbeke M, Noseda MA, Ardizzoni A, Gozzelino F, Planting A, van Zandwijk N; EORTC Lung Cancer Cooperative Group. Phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients. Eur J Cancer. 1993;29A(12):1720-2. link to original article contains protocol PubMed
- Furuse K, Kubota K, Kawahara M, Takada M, Kimura I, Fujii M, Ohta M, Hasegawa K, Yoshida K, Nakajima S, Ogura T, Niitani H; Japan Lung Cancer Vinorelbine Study Group. Phase II study of vinorelbine in heavily previously treated small cell lung cancer. Oncology. 1996 Mar-Apr;53(2):169-72. link to original article contains protocol PubMed
Maintenance after salvage therapy
Nivolumab monotherapy
back to top |
Regimen
Study | Evidence |
---|---|
Antonia et al. 2016 (CheckMate 032) | Phase I/II |
Preceding treatment
Immunotherapy
- Nivolumab (Opdivo) 3 mg/kg IV once on day 1
14-day cycles until progression or intolerance
References
- CheckMate 032: Antonia SJ, López-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, Jäger D, Pietanza MC, Le DT, de Braud F, Morse MA, Ascierto PA, Horn L, Amin A, Pillai RN, Evans J, Chau I, Bono P, Atmaca A, Sharma P, Harbison CT, Lin CS, Christensen O, Calvo E. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883-95. Epub 2016 Jun 4. link to original article contains protocol PubMed