Small cell lung cancer
Section editor | |
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Amit Kulkarni, MBBS University of Minnesota Minneapolis, MN |
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46 regimens on this page
97 variants on this page
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Guidelines
ASCO
- 2021: Daly et al. Radiation Therapy for Small-Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline
- 2020: Schneider et al. Lung Cancer Surveillance After Definitive Curative-Intent Therapy: ASCO Guideline
- 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
- 2021: Dingemans et al. Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Older
- 2013: Früh et al. Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed
NCCN
SITC
- 2022: Govindan et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lung cancer and mesothelioma
Limited stage, induction
Carboplatin & Etoposide (CE)
EP: Etoposide, Paraplatin (Carboplatin)
Regimen variant #1, 2 days of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lee et al. 2009 (LLCG-STUDY-12) | 2003-2006 | Phase 3 (C) | CE & Thalidomide, then RT | Did not meet primary endpoint of OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 100 mg PO twice per day on days 2 & 3
21-day cycle for up to 6 cycles
Subsequent treatment
- LLCG-STUDY-12, patients with PR/CR: Thoracic radiotherapy and prophylactic cranial irradiation, approximately 3 weeks after the last cycle, "according to local practice".
Regimen variant #2, 1 day of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lee et al. 2009 (LLCG-STUDY-12) | 2003-2006 | Phase 3 (C) | CE & Thalidomide, then RT | Did not meet primary endpoint of OS |
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 twice per day on day 3
21-day cycle for up to 6 cycles
Subsequent treatment
- LLCG-STUDY-12, patients with PR/CR: Thoracic radiotherapy and prophylactic cranial irradiation, approximately 3 weeks after the last cycle, "according to local practice".
References
- LLCG-STUDY-12: 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00061919
Cisplatin & Etoposide (EP)
EP: Etoposide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Evans et al. 1985 | 1981-1984 | Phase 2 |
Note: Patients with limited stage disease responding to therapy received prophylactic cranial irradiation, 4 Gy fractions 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 therapy
- Dexamethasone (Decadron) 10 mg IV once per day on days 1 to 3, prior to chemotherapy
- Metoclopramide (Reglan) 10 mg IV or PO once per day on days 1 to 3, prior to chemotherapy
- Prochlorperazine (Compazine) 10 mg IM or PO once per day on days 1 to 3, 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 dosing details in manuscript PubMed
Limited stage, definitive chemoradiotherapy
Carboplatin, Etoposide, RT
EP & RT: Etoposide, Paraplatin (Carboplatin), Radiation Therapy
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Skarlos et al. 2001 | 1993-1999 | Randomized Phase 2 (E-switch-ic) | Carboplatin, Etoposide, RT; early HTRT | Might have superior ORR |
Chemotherapy
- 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
Radiotherapy
- 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
- Skarlos et al. 2001, patients with CR: Prophylactic cranial irradiation
Regimen variant #2
Study | Evidence |
---|---|
Okamoto et al. 1999 | Phase 2 |
Eligibility criteria
- At least 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
Radiotherapy
- Thoracic radiation, given third
- Palliative radiation therapy was allowed to control persistent pain from bony metastases
Supportive therapy
- 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 (type not specified) 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 dosing details in manuscript 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; Hellenic Cooperative Oncology Group. 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 dosing details in manuscript PubMed
Cisplatin, Etoposide, RT
EP & RT: Etoposide, Platinol (Cisplatin), Radiation Therapy
PE + RT: Platinol (Cisplatin), Etoposide, Radiation Therapy
Regimen variant #1, 60/360/45
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Turrisi et al. 1999 (Intergroup 0096) | 1989-1992 | Phase 3 (E-esc) | EP & RT; once per day RT | Seems to have superior OS |
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
Radiotherapy
- Concurrent radiation therapy, 1.5 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
Regimen variant #2, 70/300/52.5, early RT
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Sun et al. 2013 (SMC 2003-02-016) | 2003-2010 | Phase 3 (C) | EP & RT; late RT | Non-inferior CR rate | Seems to have higher rates of neutropenic fever |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Radiotherapy
- Concurrent radiation therapy, 2.1 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
Regimen variant #3, 70/300/52.5, late RT
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Sun et al. 2013 (SMC 2003-02-016) | 2003-2010 | Phase 3 (E-switch-ic) | EP & RT; early RT | Non-inferior CR rate | Seems to have lower rates of neutropenic fever |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Radiotherapy
- Concurrent radiation therapy, 2.1 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
Regimen variant #4, 75/180/45, pre-planned dose reduction
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Bunn et al. 1995 | 1989-1991 | Phase 3 (C) | EP & RT; with GM-CSF support | Did not meet secondary endpoints | Less toxic |
Note: toxicity was the primary endpoint in this study.
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 3: 25 mg/m2 IV once per day on days 1 to 3
- Cycles 4 to 6: 40 mg/m2 IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1 to 3: 60 mg/m2 IV once per day on days 1 to 3
- Cycles 4 to 6: 50 mg/m2 IV once per day on days 1 to 3
Radiotherapy
- Concurrent radiation therapy during cycles 1 & 2, 1.8 Gy fractions x 25 fractions (total dose: 45 Gy)
21-day cycle for 6 cycles
Regimen variant #5, 75/300/45
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Faivre-Finn et al. 2017 (CONVERT) | 2008-2013 | Phase 3 (E-esc) | EP & RT; once per day RT | Did not meet primary endpoint of OS |
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
Radiotherapy
- Concurrent radiation therapy, 1.5 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
Regimen variant #6, 75/300/45, split doses of cisplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Faivre-Finn et al. 2017 (CONVERT) | 2008-2013 | Phase 3 (E-esc) | EP & RT; once per day RT | Did not meet primary endpoint of OS |
Chemotherapy
- 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
Radiotherapy
- Concurrent radiation therapy, 1.5 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
Regimen variant #7, 75/700/42, partially oral etoposide
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sundstrøm et al. 2002 | 1989-1994 | Phase 3 (E-switch-ic) | CEV & RT | Superior OS |
Note: Oral etoposide to be taken on an empty stomach.
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
Radiotherapy
- Concurrent thoracic radiation therapy, 2.8 Gy fractions once per day x 15 fractions (total dose: 42 Gy) over 3 weeks, given "between the third and fourth chemotherapy courses"
Supportive therapy
- "Standard prehydration and posthydration procedures were followed in conjunction with cisplatin administration."
21-day cycle for up to 5 cycles
Subsequent treatment
- Sundstrøm et al. 2002, patients with CR: Prophylactic cranial irradiation
Regimen variant #8, 80/240/50
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
McClay et al. 2005 (CALGB 9235) | 1993-1999 | Phase 3 (E-de-esc) | EP, Tamoxifen, RT | Did not meet primary endpoint of OS |
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
Radiotherapy
- Concurrent thoracic radiation therapy, 200 cGy fractions once per day x 25 fractions (total dose: 50 Gy) over 5 weeks, started on cycle 4 day 1 of chemotherapy
21-day cycle for 5 cycles
Regimen variant #9, 80/300/45, 1 cycle of chemo
Study | Dates of enrollment | Evidence |
---|---|---|
Saito et al. 2006 (WJTOG 9902) | 2000-2002 | Phase 2 |
Kubota et al. 2013 (JCOG0202) | 2002-2006 | Non-randomized part of phase 3 RCT |
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
Radiotherapy
- 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
Regimen variant #10, 80/300/45, 4 cycles of chemo
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Takada et al. 2002 (JCOG 9104) | 1991-1995 | Phase 3 (E-switch-ic) | EP, then RT | Might have superior 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
Radiotherapy
- 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
- JCOG 9104, patients with CR or near-CR ("a scar-like shadow on chest films but no positive cytology and/or bronchoscopic biopsy"): Prophylactic cranial irradiation
Regimen variant #11, 90/300/39.9
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sculier et al. 2008 | 1993-2006 | Phase 3 (E-switch-ic) | EP & RT; daily cisplatin | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 90 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Radiotherapy
- Concurrent radiation therapy, 2.66 Gy fractions once per day x 15 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 39.9 Gy)
21-day cycle for up to 6 cycles
References
- Bunn PA Jr, Crowley J, Kelly K, Hazuka MB, Beasley K, Upchurch C, Livingston R; SWOG. Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol. 1995 Jul;13(7):1632-41. Erratum in: J Clin Oncol 1995 Nov;13(11):2860. link to original article contains dosing details in manuscript 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 dosing details in manuscript 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 dosing details in manuscript 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 dosing details in manuscript PubMed
- Schild SE, Bonner JA, Shanahan TG, Brooks BJ, Marks RS, Geyer SM, Hillman SL, Farr GH Jr, Tazelaar HD, Krook JE, Geoffroy FJ, Salim M, Arusell RM, Mailliard JA, Schaefer PL, Jett JR. Long-term results of a phase III trial comparing once-daily radiotherapy with twice-daily radiotherapy in limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):943-51. link to original article PubMed
- CALGB 9235: McClay EF, Bogart J, Herndon JE 2nd, Watson D, Evans L, Seagren SL, Green MR; CALGB. A phase III trial evaluating the combination of cisplatin, etoposide, and radiation therapy with or without tamoxifen in patients with limited-stage small cell lung cancer: Cancer and Leukemia Group B Study (9235). Am J Clin Oncol. 2005 Feb;28(1):81-90. link to original article contains dosing details in abstract 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. 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 dosing details in manuscript PubMed
- Sculier JP, Lafitte JJ, Efremidis A, Florin MC, Lecomte J, Berchier MC, Richez M, Berghmans T, Scherpereel A, Meert AP, Koumakis G, Leclercq N, Paesmans M, Van Houtte P; European Lung Cancer Working Party. A phase III randomised study of concomitant induction radiochemotherapy testing two modalities of radiosensitisation by cisplatin (standard versus daily) for limited small-cell lung cancer. Ann Oncol. 2008 Oct;19(10):1691-7. Epub 2008 May 25. link to original article contains dosing details in manuscript PubMed
- SMC 2003-02-016: 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT01125995
- JCOG0202: Kubota K, Hida T, Ishikura S, Mizusawa J, Nishio M, Kawahara M, Yokoyama A, Imamura F, Takeda K, Negoro S, Harada M, Okamoto H, Yamamoto N, Shinkai T, Sakai H, Matsui K, Nakagawa K, Shibata T, Saijo N, Tamura T; JCOG. Etoposide and cisplatin versus irinotecan and cisplatin in patients with limited-stage small-cell lung cancer treated with etoposide and cisplatin plus concurrent accelerated hyperfractionated thoracic radiotherapy (JCOG0202): a randomised phase 3 study. Lancet Oncol. 2014 Jan;15(1):106-13. Epub 2013 Dec 3. link to original article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT00144989
- 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 original article link to PMC article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00433563
- CALGB 30610: https://clinicaltrials.gov/ct2/show/NCT00632853
Limited stage, adjuvant therapy
Cisplatin & Etoposide (EP)
EP: Etoposide & Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kenmotsu et al. 2020 (JCOG1205/1206) | 2013-2018 | Phase 3 (C) | Cisplatin & Irinotecan | Did not meet primary endpoint of RFS |
Preceding treatment
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
21-day cycle for up to 4 cycles
References
- JCOG1205/1206: Kenmotsu H, Niho S, Tsuboi M, Wakabayashi M, Ishii G, Nakagawa K, Daga H, Tanaka H, Saito H, Aokage K, Takahashi T, Menju T, Kasai T, Yoshino I, Minato K, Okada M, Eba J, Asamura H, Ohe Y, Watanabe SI. Randomized Phase III Study of Irinotecan Plus Cisplatin Versus Etoposide Plus Cisplatin for Completely Resected High-Grade Neuroendocrine Carcinoma of the Lung: JCOG1205/1206. J Clin Oncol. 2020 Dec 20;38(36):4292-4301. Epub 2020 Nov 2. link to original article contains dosing details in manuscript PubMed UMIN000010298
Limited stage, consolidation after upfront therapy
Cisplatin & Irinotecan (IC)
IP: Irinotecan, Platinol (Cisplatin)
Regimen
Study | Evidence |
---|---|
Saito et al. 2006 (WJTOG 9902) | Phase 2 |
Preceding treatment
- Cisplatin, Etoposide, RT induction
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 therapy
- G-CSF (no additional details given) starting after day 4
28-day cycle for 3 cycles
Subsequent treatment
- WJTOG 9902, patients with CR or good PR: 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. 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 dosing details in manuscript PubMed
Radiation therapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Evans et al. 1985 | 1981-1984 | Phase 2 |
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 dosing details in manuscript PubMed
- LLCG-STUDY-12: 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 dosing details PubMed https://clinicaltrials.gov/ct2/show/NCT00061919
Whole brain irradiation
PCI: Prophylactic Cranial Irradiation
Regimen variant #1, 20 Gy
Study | Dates of enrollment | Evidence |
---|---|---|
Cox et al. 1981 | 1975-1978 | Non-randomized |
Evans et al. 1985 | 1981-1984 | Phase 2 |
Skarlos et al. 2001 | 1993-1999 | Non-randomized part of phase 2 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 once per day x 5 fractions (total dose: 20 Gy)
1-week course
Subsequent treatment
- Evans et al. 1985: EP x 3
Regimen variant #2, 24 Gy
Study | Evidence |
---|---|
Takada et al. 2002 (JCOG 9104) | Non-randomized part of phase 3 RCT |
Radiotherapy
- Whole brain irradiation, 1.5 Gy fractions given twice per day x 16 fractions (total dose: 24 Gy)
2-week course
Regimen variant #3, 25 Gy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Turrisi et al. 1999 (Intergroup 0096) | 1989-1992 | Non-randomized part of phase 3 RCT | ||
Le Péchoux et al. 2009 (PCI 99-01/EORTC 22003-08004/RTOG 0212/IFCT 99-01) | 1999-2005 | Phase 3 (C) | PCI x 36 Gy | Did not meet primary endpoint of incidence of brain metastases at 2 years |
Saito et al. 2006 (WJTOG 9902) | 2000-2002 | Phase 2 |
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)
2-week course
Regimen variant #4, 30 Gy
Study | Evidence |
---|---|
Sundstrøm et al. 2002 | Non-randomized part of phase 3 RCT |
Radiotherapy
- Whole brain irradiation, 2 Gy fractions once per day x 15 fractions (total dose: 30 Gy)
3-week course
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 dosing details in manuscript 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 dosing details in manuscript 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 dosing details in manuscript 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 dosing details in manuscript 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. 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 dosing details in manuscript 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 https://clinicaltrials.gov/ct2/show/NCT00005062
Extensive stage, induction
Belotecan & Cisplatin
BP: Belotecan and Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Oh et al. 2016 (COMBAT) | 2009-2013 | Phase 3 (E-switch-ic) | 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00826644
Carboplatin & Etoposide (CE)
CE: Carboplatin & Etoposide
EP: Etoposide & Paraplatin (Carboplatin)
EC: Etoposide & Carboplatin
Ca/E: Carboplatin & Etoposide
Regimen variant #1, AUC 4/600, PO etoposide
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hermes et al. 2008 | 2001-2005 | Phase 3 (C) | Carboplatin & Irinotecan | Inferior OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 4 (Chatelut formula) IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 PO once per day on days 1 to 5
21-day cycle for 4 cycles
Regimen variant #2, AUC 5/240
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Okamoto et al. 2007 (JCOG 9702) | 1998-2004 | Phase 3 (E-switch-ic) | EP; split-dose | Did not meet primary endpoint of OS |
Sekine et al. 2013 (D0702002) | 2006-2007 | Phase 3 (C) | Amrubicin | Inconclusive whether non-inferior OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 3
Supportive therapy
- JCOG 9702: G-CSF
21-day cycle for 4 to 6 cycles
Regimen variant #3, AUC 5/300, 21-day cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Socinski et al. 2009 (JMHO) | 2006-2007 | Phase 3 (C) | Carboplatin & Pemetrexed | Superior OS |
Spigel et al. 2011 (SALUTE) | 2007-2008 | Randomized Phase 2 (C) | 1a. CE & Bevacizumab 1b. EP & Bevacizumab |
Seems to have inferior PFS |
Ready et al. 2015 (CALGB 30504) | 2007-2011 | Non-randomized part of phase 2 RCT | ||
Reck et al. 2016 (CA184-156) | 2012-2014 | Phase 3 (C) | 1a. CE & Ipilimumab 1b. EP & Ipilimumab |
Did not meet primary endpoint of OS |
Jalal et al. 2017 (MATISSE) | 2012-2013 | Randomized Phase 2 (C) | PaCE | Might have superior OS |
Horn et al. 2018 (IMpower133) | 2016-2017 | Phase 3 (C) | CE & Atezolizumab | Seems to have inferior OS1 |
Paz-Ares et al. 2019 (CASPIAN) | 2017-03-27 to 2018-05-29 | Phase 3 (C) | 1a. CE & Durvalumab 1b. EP & Durvalumab |
Inferior OS |
Rudin et al. 2020 (KEYNOTE-604) | 2017-2018 | Phase 3 (C) | 1a. CE & Pembrolizumab 1b. EP & Pembrolizumab |
Seems to have inferior OS |
Wang et al. 2022 (CAPSTONE-1) | 2018-2020 | Phase 3 (C) | CE & Adebrelimab | Inferior OS |
1Reported efficacy for IMpower133 is based on the 2020 update.
Note: CASPIAN gave a range of dosing; see paper for details.
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 therapy
- 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
Regimen variant #4, AUC 5/300, 28-day cycles
Study | Dates of enrollment | Evidence |
---|---|---|
Okamoto et al. 1999 | 1995-1996 | Phase 2 |
Quoix et al. 2001 | 1997-1999 | Phase 2 |
Eligibility criteria
- At least 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
Supportive therapy
- 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
- Okamoto et al. 1999: G-CSF (type not specified) 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
Subsequent treatment
- Palliative radiation therapy was allowed to control persistent pain from bony metastases
Regimen variant #5, AUC 5/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
21-day cycle for 6 cycles
Regimen variant #6, AUC 5/420
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Heigener et al. 2009 | 2000-2003 | Phase 3 (C) | CE; dose-intense | Did not meet primary endpoint of OS |
Schmittel et al. 2006 | 2002-2008 | Randomized Phase 2 (E-switch-ic) | IP | Might have inferior OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1
- Etoposide (Vepesid) 140 mg/m2 IV over 90 minutes once per day on days 1 to 3
Supportive therapy
- 5-HT3 antagonist IV once per day on days 1 to 3, prior to chemotherapy
- Loperamide (Imodium) 4 mg PO prn first episode of diarrhea, then 2 mg PO Q2H until diarrhea stops
21- to 28-day cycle for up to 6 cycles
Regimen variant #7, AUC 5/440, 1 day of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lee et al. 2009 (LLCG-STUDY-12) | 2003-2006 | Phase 3 (C) | CE & Thalidomide | Did not meet primary endpoint of OS |
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3
21-day cycle for up to 6 cycles
Regimen variant #8, AUC 5/520, 2 days of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lee et al. 2009 (LLCG-STUDY-12) | 2003-2006 | Phase 3 (C) | CE & Thalidomide | Did not meet primary endpoint of OS |
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 100 mg PO twice per day on days 2 & 3
21-day cycle for up to 6 cycles
Regimen variant #9, AUC 6/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
21-day cycle for 6 cycles
Regimen variant #10, AUC 6/440, 1 day of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS |
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 twice per day on day 3
21-day cycle for up to 6 cycles
Regimen variant #11, AUC 6/520, 2 days of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 100 mg PO twice per day on days 2 & 3
21-day cycle for up 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 dosing details in manuscript 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 dosing details in manuscript 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 dosing details in manuscript 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 dosing details in manuscript PubMed
- JCOG 9702: Okamoto H, Watanabe K, Kunikane H, Yokoyama A, Kudoh S, Asakawa T, Shibata T, Kunitoh H, Tamura T, Saijo N. Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer. 2007 Jul 16;97(2):162-9. Epub 2007 Jun 19. link to original article link to PMC article contains dosing details in abstract PubMed
- Hermes A, Bergman B, Bremnes R, Ek L, Fluge S, Sederholm C, Sundstrøm S, Thaning L, Vilsvik J, Aasebø U, Sörenson S. Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial. J Clin Oncol. 2008 Sep 10;26(26):4261-7. link to original article contains dosing details in abstract PubMed
- Heigener DF, Manegold C, Jäger E, Saal JG, Zuna I, Gatzemeier U. Multicenter randomized open-label phase III study comparing efficacy, safety, and tolerability of conventional carboplatin plus etoposide versus dose-intensified carboplatin plus etoposide plus lenograstim in small-cell lung cancer in "extensive disease" stage. Am J Clin Oncol. 2009 Feb;32(1):61-4. link to original article contains dosing details in abstract PubMed
- LLCG-STUDY-12: 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00061919
- JMHO: 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00363415
- 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00403403
- D0702002: 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 dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT00286169
- 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00453154
- CA184-156: Reck M, Luft A, Szczesna A, Havel L, Kim SW, Akerley W, Pietanza MC, Wu YL, Zielinski C, Thomas M, Felip E, Gold K, Horn L, Aerts J, Nakagawa K, Lorigan P, Pieters A, Kong Sanchez T, Fairchild J, Spigel D. Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer. J Clin Oncol. 2016 Nov 1;34(31):3740-3748. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT01450761
- 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 dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT00433498
- 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT01555710
- IMpower133: Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. Epub 2018 Sep 25. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT02763579
- PRO analysis: Mansfield AS, Każarnowicz A, Karaseva N, Sánchez A, De Boer R, Andric Z, Reck M, Atagi S, Lee JS, Garassino M, Liu SV, Horn L, Wen X, Quach C, Yu W, Kabbinavar F, Lam S, Morris S, Califano R. Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Ann Oncol. 2020 Feb;31(2):310-317. Epub 2019 Dec 9. link to original article PubMed
- Update: Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. Epub 2021 Jan 13. link to original article link to PMC article PubMed
- CASPIAN: Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. Epub 2019 Oct 4. link to original article PubMed https://clinicaltrials.gov/ct2/show/NCT03043872
- PRO analysis: Goldman JW, Garassino MC, Chen Y, Özgüroğlu M, Dvorkin M, Trukhin D, Statsenko G, Hotta K, Ji JH, Hochmair MJ, Voitko O, Havel L, Poltoratskiy A, Losonczy G, Reinmuth N, Patel N, Laud PJ, Shire N, Jiang H, Paz-Ares L. Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Lung Cancer. 2020 Nov;149:46-52. Epub 2020 Sep 10. link to original article PubMed
- Update: Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. Epub 2020 Dec 4. link to original article PubMed
- KEYNOTE-604: Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. link to original article link to PMC article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT03066778
- CAPSTONE-1: Wang J, Zhou C, Yao W, Wang Q, Min X, Chen G, Xu X, Li X, Xu F, Fang Y, Yang R, Yu G, Gong Y, Zhao J, Fan Y, Liu Q, Cao L, Yao Y, Liu Y, Li X, Wu J, He Z, Lu K, Jiang L, Hu C, Zhao W, Zhang B, Shi W, Zhang X, Cheng Y; CAPSTONE-1 Study Group. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Jun;23(6):739-747. Epub 2022 May 13. link to original article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT03711305
Carboplatin & Etoposide (CE) & Atezolizumab
CE & Atezolizumab: Carboplatin, Etoposide, Atezolizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | |
---|---|---|---|---|---|
Horn et al. 2018 (IMpower133)
|
2016-2017 | Phase 3 (E-RT-esc) | CE | Seems to have superior OS1 (co-primary endpoint) Median OS: 12.3 vs 10.3 mo (HR 0.76, 95% CI 0.60-0.95) |
1Reported efficacy for IMpower133 is based on the 2020 update.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1 to 4: 100 mg/m2 IV once per day on days 1 to 3
Immunotherapy
- Atezolizumab (Tecentriq) 1200 mg IV once on day 1
21-day cycles
References
- IMpower133: Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. Epub 2018 Sep 25. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT02763579
- PRO analysis: Mansfield AS, Każarnowicz A, Karaseva N, Sánchez A, De Boer R, Andric Z, Reck M, Atagi S, Lee JS, Garassino M, Liu SV, Horn L, Wen X, Quach C, Yu W, Kabbinavar F, Lam S, Morris S, Califano R. Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Ann Oncol. 2020 Feb;31(2):310-317. Epub 2019 Dec 9. link to original article PubMed
- Update: Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. Epub 2021 Jan 13. link to original article link to PMC article PubMed
- IMforte: https://clinicaltrials.gov/ct2/show/NCT05091567
Carboplatin & Etoposide (CE) & Bevacizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Spigel et al. 2011 (SALUTE) | 2007-2008 | Randomized Phase 2 (E-esc) | 1a. CE 1b. EP |
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
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Bevacizumab maintenance
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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00403403
Carboplatin & Etoposide (CE) & Durvalumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | |
---|---|---|---|---|---|
Paz-Ares et al. 2019 (CASPIAN)
|
2017-03-27 to 2018-05-29 | Phase 3 (E-RT-esc) | 1a. CE 1b. EP |
Superior OS1 (primary endpoint) Median OS: 12.9 vs 10.5 mo (HR 0.75, 95% CI 0.62-0.91) |
1Reported efficacy is based on the 2021 update.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 to 6 IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1 to 4: 80 to 100 mg/m2 IV once per day on days 1 to 3
Immunotherapy
- Durvalumab (Imfinzi) 1500 mg IV once on day 1
21-day cycle for 4 cycles, then 28-day cycles
References
- CASPIAN: Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. Epub 2019 Oct 4. link to original article PubMed https://clinicaltrials.gov/ct2/show/NCT03043872
- PRO analysis: Goldman JW, Garassino MC, Chen Y, Özgüroğlu M, Dvorkin M, Trukhin D, Statsenko G, Hotta K, Ji JH, Hochmair MJ, Voitko O, Havel L, Poltoratskiy A, Losonczy G, Reinmuth N, Patel N, Laud PJ, Shire N, Jiang H, Paz-Ares L. Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Lung Cancer. 2020 Nov;149:46-52. Epub 2020 Sep 10. link to original article PubMed
- Update: Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. Epub 2020 Dec 4. link to original article PubMed
Carboplatin & Etoposide (CE) & Serplulimab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cheng et al. 2022 (ASTRUM-005) | 2019-09-12 to 2021-04-27 | Phase 3 (E-esc) | CE | Superior OS Median OS: 15.4 vs 10.9 mo (HR 0.63, 95% CI 0.49-0.82) |
Note: the original capped dose of carboplatin was 800 mg; this was modified in a protocol amendment.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 (maximum dose of 750 mg) IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1 to 4: 100 mg/m2 IV once per day on days 1 to 3
Immunotherapy
- Serplulimab (Hansizhuang) 4.5 mg/kg IV once on day 1
21-day cycles
References
- ASTRUM-005: Cheng Y, Han L, Wu L, Chen J, Sun H, Wen G, Ji Y, Dvorkin M, Shi J, Pan Z, Shi J, Wang X, Bai Y, Melkadze T, Pan Y, Min X, Viguro M, Li X, Zhao Y, Yang J, Makharadze T, Arkania E, Kang W, Wang Q, Zhu J; ASTRUM-005 Study Group. Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial. JAMA. 2022 Sep 27;328(12):1223-1232. link to original article contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT04063163
Carboplatin & Irinotecan
IC: Irinotecan & Carboplatin
IP: Irinotecan & Paraplatin (Carboplatin)
Regimen variant #1, AUC 4/175
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hermes et al. 2008 | 2001-2005 | Phase 3 (E-switch-ic) | CE | Superior OS Median OS: 8.5 vs 7.1 mo (HR 0.71, 95% CI 0.53-0.94) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 4 (Chatelut formula) IV once on day 1
- Irinotecan (Camptosar) 175 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Regimen variant #2, AUC 5/150
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schmittel et al. 2006 | 2002-2008 | Randomized Phase 2 (E-switch-ic) | CE | Might have superior OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1
- Irinotecan (Camptosar) 50 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
Supportive therapy
- 5-HT3 antagonist IV once per day on days 1, 8, 15, prior to 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 dosing details in manuscript 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 dosing details in manuscript PubMed
- Hermes A, Bergman B, Bremnes R, Ek L, Fluge S, Sederholm C, Sundstrøm S, Thaning L, Vilsvik J, Aasebø U, Sörenson S. Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial. J Clin Oncol. 2008 Sep 10;26(26):4261-7. link to original article contains dosing details in abstract PubMed
Carboplatin & Paclitaxel (CP) & Ipilimumab
Regimen variant #1, phased ipilimumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Reck et al. 2012 (CA184-041) | 2008-2009 | Randomized Phase 2 (E-esc) | 1. CP | Seems to have superior irPFS |
2. CP & Ipilimumab; concurrent Ipilimumab | Not reported |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
Immunotherapy
- Ipilimumab (Yervoy) as follows:
- Cycles 3 to 6: 10 mg/kg IV once on day 1
21-day cycle for up to 6 cycles
Subsequent treatment
- Ipilimumab maintenance
Regimen variant #2, concurrent ipilimumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Reck et al. 2012 (CA184-041) | 2008-2009 | Randomized Phase 2 (E-esc) | 1. CP | Did not meet secondary endpoints |
2. CP & Ipilimumab; phased Ipilimumab | Not reported |
Note: all efficacy endpoints in the ED-SCLC cohort were secondary.
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
Immunotherapy
- Ipilimumab (Yervoy) as follows:
- Cycles 1 to 4: 10 mg/kg IV once on day 1
21-day cycle for up to 6 cycles
Subsequent treatment
- Ipilimumab maintenance
References
- CA184-041: 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. Epub 2012 Aug 2. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00527735
Cisplatin & Etoposide (EP)
EP: Etoposide and Platinol (Cisplatin)
PE: Platinol (Cisplatin) and Etoposide
Regimen variant #1, 60/300
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Oh et al. 2016 (COMBAT) | 2009-2013 | Phase 3 (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
Regimen variant #2, 60/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hanna et al. 2006 | 2000-2003 | Phase 3 (C) | Cisplatin & Irinotecan | Did not meet primary endpoint of OS |
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS |
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 therapy
- 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
Regimen variant #3, 60/440, 1 day of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS |
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 twice per day on day 3
21-day cycle for up to 6 cycles
Regimen variant #4, 60/520, 2 days of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS |
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 twice per day on days 2 & 3
21-day cycle for up to 6 cycles
Regimen variant #5, 70/300
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ruotsalainen et al. 1999 | NR in abstract | Phase 3 (C) | EP & IFN-alpha | Did not meet endpoint of OS50% |
Kim et al. 2018 (CRCST-L-0001) | 2006-2011 | Phase 3 (C) | Cisplatin & Irinotecan | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 70 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 up to 6 cycles
Regimen variant #6, 75/240, split cisplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Okamoto et al. 2007 (JCOG 9702) | 1998-2004 | Phase 3 (C) | CE | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1 to 3
- Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 3
21- to 28-day cycle for 4 cycles
Regimen variant #7, 75/300
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ignatiadis et al. 2005 | 2000-2003 | Phase 3 (C) | EP/Topotecan | Did not meet primary endpoint of OS |
Fink et al. 2012 (GSK 104864-A/479) | 2002-2006 | Phase 3 (C) | 1. Cisplatin & Topotecan | Non-inferior OS |
2. Etoposide & Topotecan | Not reported | |||
Spigel et al. 2011 (SALUTE) | 2007-2008 | Randomized Phase 2 (C) | 1a. CE & Bevacizumab 1b. EP & Bevacizumab |
Seems to have inferior PFS |
Reck et al. 2016 (CA184-156) | 2012-2014 | Phase 3 (C) | 1a. CE & Ipilimumab 1b. EP & Ipilimumab |
Did not meet primary endpoint of OS |
Rudin et al. 2020 (KEYNOTE-604) | 2017-2018 | Phase 3 (C) | 1a. CE & Pembrolizumab 1b. EP & Pembrolizumab |
Seems to have inferior OS |
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 & KEYNOTE-604) or 6 (GSK 104864-A/479 & CA184-156) cycles
Regimen variant #8, 75/300, split cisplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Evans et al. 1985 | 1981-1984 | Phase 2 | ||
Tiseo et al. 2017 (GOIRC-AIFA FARM6PMFJM) | 2009-2015 | Phase 3 (C) | EP & Bevacizumab | Did not meet primary endpoint of OS |
Note: in Evans et al. 1985, 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.
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 therapy
- Dexamethasone (Decadron) 10 mg IV once per day on days 1 to 3, prior to chemotherapy
- Metoclopramide (Reglan) 10 mg IV or PO once per day on days 1 to 3, prior to chemotherapy
- Prochlorperazine (Compazine) 10 mg IM or PO once per day on days 1 to 3, 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 up to 6 cycles
Regimen variant #9, 75/390, split cisplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Miller et al. 1995 | 1990-1993 | Phase 3 (C) | EP; oral etoposide | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1 to 3
- Etoposide (Vepesid) 130 mg/m2 IV once per day on days 1 to 3
21-day cycle for 8 cycles
Regimen variant #10, 75/700, 3 days of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sundstrøm et al. 2002 | 1989-1994 | Phase 3 (E-switch-ic) | CEV | Did not meet primary endpoint of OS |
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." Oral etoposide to be taken on an empty stomach.
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
Supportive therapy
- "Standard prehydration and posthydration procedures were followed in conjunction with cisplatin administration."
21-day cycle for up to 5 cycles
Regimen variant #11, 80/240
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ihde et al. 1994 | 1983-1991 | Phase 3 (C) | EP; high-dose | Did not meet primary endpoint of CR rate |
Niell et al. 2005 (CALGB 9732) | 1998-2001 | Phase 3 (C) | PET | Did not meet endpoints of FFS50%/OS50% |
Note: Concurrent radiation therapy with the start of chemotherapy was given to patients with brain metastases, epidural metastases, and impending pathologic bone fractures.
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
Supportive therapy
- "Half-normal saline was infused for 2 to 6 hours with cisplatin, 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
CNS therapy
- Patients with carcinomatous meningitis received Methotrexate (MTX) IT (dose/schedule not specified) and radiation to functionally compromised areas of the CNS
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."
Regimen variant #12, 80/300
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fukuoka et al. 1991 (JCOG8502) | 1985-1988 | Phase 3 (C) | 1. CAV | Not reported |
2. CAV/PE | Might have inferior OS | |||
Miyamoto et al. 1992 | NR in abstract | Phase 3 (C) | PEI | Did not meet primary endpoint of OS |
Noda et al. 2002 (JCOG 9511) | 1995-1998 | Phase 3 (C) | IP | Inferior OS |
Eckardt et al. 2006 (GSK 104864-A/389) | 2001-2003 | Phase 3 (C) | Cisplatin & Topotecan | Non-inferior OS |
Lara et al. 2009 (SWOG S0124) | 2002-2007 | Phase 3 (C) | IP | Did not meet primary endpoint of OS |
Baka et al. 2010 | 2002-2006 | Phase 3 (C) | EP/T | Did not meet primary endpoint of OS |
Zatloukal et al. 2010 | 2003-2007 | Phase 3 (C) | IP | Non-inferior OS |
Ready et al. 2015 (CALGB 30504) | 2007-2011 | Non-randomized part of phase 2 RCT | ||
Sun et al. 2016 (D0750018) | 2008-2010 | Phase 3 (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
- JCOG8502 & Miyamoto et al. 1992 gave etoposide on days 1, 3, 5
Supportive therapy
- "Hydration and administration of antiemetic drugs."
21-day cycle for 4 to 6 cycles
Subsequent treatment
- Baka et al. 2010: Topotecan x 4
- CALGB 30504, SD or better: Observation versus sunitinib maintenance
Regimen variant #13, 80/400, split cisplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Loehrer et al. 1995 | 1989-1993 | Phase 3 (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
Regimen variant #14, 80/600, 2 days of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baka et al. 2008 | 1999-2005 | Phase 3 (E-switch-ic) | ACE | Did not meet primary endpoint of OS12 |
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
Regimen variant #15, 100/300
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Artal-Cortés et al. 2004 | 1994-1998 | Phase 3 (C) | Cisplatin & Epirubicin | Did not meet primary endpoint of OS |
Pujol et al. 2001 (FNCLCC 95012) | 1996-1999 | Phase 3 (C) | PCDE | Inferior OS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 2
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for 6 cycles
Regimen variant #16, 100/400, split cisplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Roth et al. 1992 | 1985-1989 | Phase 3 (C) | 1. CAV 2. CAV/PE |
Did not meet primary endpoint of OS50% |
Hainsworth et al. 1995 | 1992-1993 | Randomized Phase 2 (E-RT-switch-ic) | Cisplatin & Etoposide phosphate | Not compared |
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 dosing details in manuscript PubMed
- JCOG8502: 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 dosing details in abstract PubMed
- Miyamoto H, Nakabayashi T, Isobe H, Akita H, Kawakami Y, Arimoto T, Asakawa M, Suzuki A, Fujikane T, Shimizu T, Sakai E. A phase III comparison of etoposide/cisplatin with or without added ifosfamide in small-cell lung cancer. Oncology. 1992;49(6):431-5. link to original article contains dosing details in abstract 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; Southeastern Cancer Study Group. 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 dosing details in manuscript 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 dosing details in manuscript PubMed
- Hainsworth JD, Levitan N, Wampler GL, Belani CP, Seyedsadr MS, Randolph J, Schacter LP, Greco FA. Phase II randomized study of cisplatin plus etoposide phosphate or etoposide in the treatment of small-cell lung cancer. J Clin Oncol. 1995 Jun;13(6):1436-42. link to original article PubMed
- Miller AA, Herndon JE 2nd, Hollis DR, Ellerton J, Langleben A, Richards F 2nd, Green MR; CALGB. Schedule dependency of 21-day oral versus 3-day intravenous etoposide in combination with intravenous cisplatin in extensive-stage small-cell lung cancer: a randomized phase III study of the Cancer and Leukemia Group B. J Clin Oncol. 1995 Aug;13(8):1871-9. link to original article contains dosing details in abstract PubMed
- Loehrer PJ Sr, Ansari R, Gonin R, Monaco F, Fisher W, Sandler A, Einhorn LH; Hoosier Oncology Group. 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 dosing details in manuscript PubMed
- Ruotsalainen TM, Halme M, Tamminen K, Szopinski J, Niiranen A, Pyrhönen S, Riska H, Maasilta P, Jekunen A, Mäntylä M, Kajanti M, Joensuu H, Sarna S, Cantell K, Mattson K. Concomitant chemotherapy and IFN-alpha for small cell lung cancer: a randomized multicenter phase III study. J Interferon Cytokine Res. 1999 Mar;19(3):253-9. link to original article contains dosing details in abstract PubMed
- FNCLCC 95012: Pujol JL, Daurès JP, Rivière A, Quoix E, Westeel V, Quantin X, Breton JL, Lemarié E, Poudenx M, Milleron B, Moro D, Debieuvre D, Le Chevalier T. Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study. J Natl Cancer Inst. 2001 Feb 21;93(4):300-8. link to original article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT00003606
- 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; JCOG. 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 dosing details in manuscript 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 dosing details in manuscript PubMed
- Artal-Cortés A, Gomez-Codina J, Gonzalez-Larriba JL, Barneto I, Carrato A, Isla D, Camps C, Garcia-Giron C, Font A, Meana A, Lomas M, Vadell C, Arrivi A, Alonso C, Maestu I, Campbell J, Rosell R. Prospective randomized phase III trial of etoposide/cisplatin versus high-dose epirubicin/cisplatin in small-cell lung cancer. Clin Lung Cancer. 2004 Nov;6(3):175-83. link to original article contains dosing details in abstract PubMed
- CALGB 9732: 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; CALGB. 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00003299
- Ignatiadis M, Mavroudis D, Veslemes M, Boukovinas J, Syrigos K, Agelidou M, Agelidou A, Gerogianni A, Pavlakou G, Tselepatiotis E, Nikolakopoulos J, Georgoulias V; Hellenic Oncology Research Group. Sequential versus alternating administration of cisplatin/etoposide and topotecan as first-line treatment in extensive-stage small-cell lung cancer: preliminary results of a Phase III Trial of the Hellenic Oncology Research Group. Clin Lung Cancer. 2005 Nov;7(3):183-9. link to original article contains dosing details in abstract 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 dosing details in manuscript PubMed
- GSK 104864-A/389: 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 dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT00043927
- JCOG 9702: Okamoto H, Watanabe K, Kunikane H, Yokoyama A, Kudoh S, Asakawa T, Shibata T, Kunitoh H, Tamura T, Saijo N. Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer. 2007 Jul 16;97(2):162-9. Epub 2007 Jun 19. link to original article link to PMC article contains dosing details in abstract 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 dosing details in abstract 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00045162
- 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00143455
- Baka S, Agelaki S, Kotsakis A, Veslemes M, Papakotoulas P, Agelidou M, Agelidou A, Tsaroucha E, Pavlakou G, Gerogianni A, Androulakis N, Vamvakas L, Kalbakis K, Mavroudis D, Georgoulias V. Phase III study comparing sequential versus alternate administration of cisplatin-etoposide and topotecan as first-line treatment in small cell lung cancer. Anticancer Res. 2010 Jul;30(7):3031-8. link to original article contains dosing details in abstract 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00403403
- GSK 104864-A/479: 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 dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT00320359
- 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00453154
- D0750018: 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00660504
- 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00826644
- CA184-156: Reck M, Luft A, Szczesna A, Havel L, Kim SW, Akerley W, Pietanza MC, Wu YL, Zielinski C, Thomas M, Felip E, Gold K, Horn L, Aerts J, Nakagawa K, Lorigan P, Pieters A, Kong Sanchez T, Fairchild J, Spigel D. Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer. J Clin Oncol. 2016 Nov 1;34(31):3740-3748. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT01450761
- GOIRC-AIFA FARM6PMFJM: Tiseo M, Boni L, Ambrosio F, Camerini A, Baldini E, Cinieri S, Brighenti M, Zanelli F, Defraia E, Chiari R, Dazzi C, Tibaldi C, Turolla GM, D'Alessandro V, Zilembo N, Trolese AR, Grossi F, Riccardi F, Ardizzoni A. Italian, multicenter, phase III, randomized study of cisplatin plus etoposide with or without bevacizumab as first-line treatment in extensive-disease small-cell lung cancer: the GOIRC-AIFA FARM6PMFJM trial. J Clin Oncol. 2017 Apr 20;35(12):1281-1287. Epub 2017 Jan 30. link to original article contains dosing details in manuscript PubMed EudraCT 2007-007949-13
- 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 dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT00433498
- CRCST-L-0001: Kim DW, Kim HG, Kim JH, Park K, Kim HK, Jang JS, Kim BS, Kang JH, Lee KH, Kim SW, Ryoo HM, Kim JS, Lee KH, Kwon JH, Choi JH, Shin SW, Hahn S, Heo DS. Randomized phase III trial of irinotecan plus cisplatin versus etoposide plus cisplatin in chemotherapy-naïve Korean patients with extensive-disease small cell lung cancer. Cancer Res Treat. 2019 Jan;51(1):119-127. Epub 2018 Mar 12. link to original article link to PMC article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT00349492
- KEYNOTE-604: Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. link to original article link to PMC article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT03066778
Cisplatin & Etoposide (EP) & Bevacizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Spigel et al. 2011 (SALUTE) | 2007-2008 | Randomized Phase 2 (E-esc) | 1a. CE 1b. EP |
Seems to have superior PFS Median PFS: 5.5 vs 4.4 mo (HR 0.53, 95% CI 0.32-0.86) |
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
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Bevacizumab maintenance
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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00403403
Cisplatin & Etoposide (EP) & Durvalumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | |
---|---|---|---|---|---|
Paz-Ares et al. 2019 (CASPIAN)
|
2017-03-27 to 2018-05-29 | Phase 3 (E-RT-esc) | 1a. CE 1b. EP |
Superior OS1 (primary endpoint) Median OS: 12.9 vs 10.5 mo (HR 0.75, 95% CI 0.62-0.91) |
1Reported efficacy is based on the 2021 update.
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 4: 75 to 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1 to 4: 80 to 100 mg/m2 IV once per day on days 1 to 3
Immunotherapy
- Durvalumab (Imfinzi) 1500 mg IV once on day 1
21-day cycle for 4 cycles, then 28-day cycles
References
- CASPIAN: Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. Epub 2019 Oct 4. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT03043872
- PRO analysis: Goldman JW, Garassino MC, Chen Y, Özgüroğlu M, Dvorkin M, Trukhin D, Statsenko G, Hotta K, Ji JH, Hochmair MJ, Voitko O, Havel L, Poltoratskiy A, Losonczy G, Reinmuth N, Patel N, Laud PJ, Shire N, Jiang H, Paz-Ares L. Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Lung Cancer. 2020 Nov;149:46-52. Epub 2020 Sep 10. link to original article PubMed
- Update: Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. Epub 2020 Dec 4. link to original article PubMed
Cisplatin & Irinotecan (IC)
IP: Irinotecan, Platinol (Cisplatin)
Regimen variant #1, 30/65
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hanna et al. 2006 | 2000-2003 | Phase 3 (E-switch-ic) | Cisplatin & Etoposide | Did not meet primary endpoint of OS |
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 therapy
- 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
Regimen variant #2, 60/60
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Noda et al. 2002 (JCOG 9511) | 1995-1998 | Phase 3 (E-switch-ic) | EP | Superior OS |
Lara et al. 2009 (SWOG S0124) | 2002-2007 | Phase 3 (E-switch-ic) | EP | Did not meet primary endpoint of OS |
Satouchi et al. 2014 (JCOG 0509) | 2007-2010 | Phase 3 (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 therapy
- "Hydration and administration of antiemetic drugs."
28-day cycle for 4 cycles
Regimen variant #3, 80/65
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zatloukal et al. 2010 | 2003-2007 | Phase 3 (E-switch-ic) | EP | Non-inferior OS |
Note: this dosing was the result of a mid-protocol amendment.
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; JCOG. 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 dosing details in manuscript 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 dosing details in manuscript 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00045162
- 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00143455
- 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 dosing details in manuscript PubMed UMIN000000720
Docetaxel monotherapy
Regimen
Study | Evidence |
---|---|
Hesketh et al. 1999 | Phase 2 |
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; SWOG. 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 dosing details in abstract PubMed
Ifosfamide monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Ettinger et al. 2002 (ECOG E1588) | 1988-1990 | Phase 3 (E-switch-ic) | 1. CAV | Did not meet primary endpoint of OS | Less toxic |
2. Teniposide | Did not meet primary endpoint of OS | Not reported |
Chemotherapy
- Ifosfamide (Ifex) 1500 mg/m2 IV once per day on days 1 to 5
Supportive therapy
- Mesna (Mesnex) 300 mg/m2 IV three times per day on days 1 to 5, given 0, 4, and 8 hours after each dose of ifosfamide (total dose per cycle: 4500 mg/m2)
21-day cycle for 4 to 6 cycles
Subsequent treatment
- ECOG E1588, patients with CR: another 2 cycles of ifosfamide, then prophylactic whole-brain irradiation if still in CR
- ECOG E1588, patients with PR: ifosfamide until progression of disease, then salvage EP
References
- ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; ECOG. 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 dosing details in manuscript PubMed
IVE
IVE: Ifosfamide, VP-16 (Etoposide), Epirubicin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Berghmans et al. 2017 (ELCWP 01994) | 2000-2013 | Phase 3 (C) | EP | Did not meet primary endpoint of OS |
Note: This combination is based on a commonly used backbone in Europe. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Chemotherapy
- Ifosfamide (Ifex) 1500 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
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
Supportive therapy
- Mesna (Mesnex) 300 mg/m2 IV once on day 1, given just before ifosfamide, then 300 mg/m2 IV once every 4 hours for 72 hours (total dose per cycle: 5700 mg/m2)
21-day cycles
References
- ELCWP 01994: Berghmans T, Scherpereel A, Meert AP, Giner V, Lecomte J, Lafitte JJ, Leclercq N, Paesmans M, Sculier JP; European Lung Cancer Working Party (ELCWP). A Phase III Randomized Study Comparing a Chemotherapy with Cisplatin and Etoposide to a Etoposide Regimen without Cisplatin for Patients with Extensive Small-Cell Lung Cancer. Front Oncol. 2017 Sep 19;7:217. link to original article link to PMC article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00658580
Teniposide monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Ettinger et al. 2002 (ECOG E1588) | 1988-1990 | Phase 3 (E-switch-ic) | 1. CAV | Did not meet primary endpoint of OS | Less toxic |
2. Ifosfamide | Did not meet primary endpoint of OS | 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
- ECOG E1588, patients with CR after 4 to 6 cycles: another 2 cycles of teniposide
- ECOG E1588, patients with CR after 6 to 8 cycles: prophylactic whole-brain irradiation
- ECOG E1588, patients with PR: teniposide until progression of disease, then salvage EP
References
- ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; ECOG. 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 dosing details in manuscript PubMed
Extensive stage, consolidation after first-line therapy
Whole brain irradiation
PCI: Prophylactic Cranial Irradiation
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ettinger et al. 2002 (ECOG E1588) | 1988-1990 | Non-randomized part of phase 3 RCT | ||
Slotman et al. 2007 (EORTC 22993) | 2001-2006 | Phase 3 (E-esc) | Observation | Superior OS Median OS: 6.7 vs 5.4 mo (HR 0.68, 95% CI 0.52-0.88) |
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
1- to 3-week 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; ECOG. 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 dosing details in manuscript 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; EORTC 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 dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT00016211
Extensive stage, maintenance after first-line therapy
Bevacizumab monotherapy
Regimen
Study | Evidence |
---|---|
Spigel et al. 2011 (SALUTE) | Non-randomized part of phase 2 RCT |
Preceding treatment
- CE & Bevacizumab induction x 4 or EP & Bevacizumab induction x 4
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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00403403
Ipilimumab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Reck et al. 2012 (CA184-041) | 2008-2009 | Non-randomized part of phase 2 RCT |
Preceding treatment
- Carboplatin, Paclitaxel, Ipilimumab induction
References
- CA184-041: 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. Epub 2012 Aug 2. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00527735
Sunitinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ready et al. 2015 (CALGB 30504) | 2007-2011 | Randomized Phase 2 (E-esc) | Observation | Seems to have superior PFS |
Preceding treatment
- Carboplatin & Etoposide or Cisplatin & Etoposide for 4 to 6 cycles
Targeted therapy
- 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00453154
Relapsed or refractory disease, second-line
Amrubicin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Pawel et al. 2014 (ACT-1) | 2007-2010 | Phase 3 (E-switch-ic) | Topotecan | Did not meet primary endpoint of OS Median OS: 7.5 vs 7.8 mo (HR 0.88, 95% CI 0.73-1.06) |
Spigel et al. 2021 (CheckMate 331) | 2015-2017 | Phase 3 (C) | Nivolumab | Might have inferior OS |
Chemotherapy
- Amrubicin (Calsed) 40 mg/m2 IV over 5 minutes once per day on days 1 to 3
Supportive therapy
- "Prophylactic antibiotics were recommended for patients at high risk of infectious complications."
21-day cycle for at least 6 cycles
References
- ACT-1: 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00547651
- CheckMate 331: Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, Audigier-Valette C, Pardo Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331. Ann Oncol. 2021 May;32(5):631-641. Epub 2021 Feb 1. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT02481830
Carboplatin & Etoposide (CE)
EC: Etoposide & Carboplatin
EP: Etoposide & Paraplatin (Carboplatin)
CE: Carboplatin & Etoposide
Ca/E: Carboplatin & Etoposide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baize et al. 2020 (GFPC 01-2013) | 2013-2018 | Phase 3 (E-switch-ic) | Topotecan | Superior PFS Median PFS: 4.7 vs 2.7 mo (HR 0.57, 90% CI 0.41-0.73) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for 6 cycles
References
- GFPC 01-2013: Baize N, Monnet I, Greillier L, Geier M, Lena H, Janicot H, Vergnenegre A, Crequit J, Lamy R, Auliac JB, Letreut J, Le Caer H, Gervais R, Dansin E, Madroszyk A, Renault PA, Le Garff G, Falchero L, Berard H, Schott R, Saulnier P, Chouaid C; Groupe Français de Pneumo-Cancérologie. Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1224-1233. link to original article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT02738346
Cisplatin, Etoposide, Irinotecan
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Goto et al. 2016 (JCOG0605) | 2007-2012 | Phase 3 (E-esc) | Topotecan | Superior OS Median OS: 18.2 vs 12.5 mo (HR 0.67, 90% CI 0.51-0.88) |
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 therapy
- G-CSF, started on cycle 1 day 9: (dose not specified) SC once per day, continued throughout except for days of chemotherapy
14-day cycle for 5 cycles
References
- JCOG0605: 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; JCOG. 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 dosing details in abstract PubMed UMIN000000828
Lurbinectedin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Efficacy | |
---|---|---|---|---|
Trigo et al. 2020 (PM1183-B-005-14)
|
2015-2019 | Phase 2 (RT) | ORR: 35.2% (95% CI, 26.2-45.2%) |
Chemotherapy
- Lurbinectedin (Zepzelca) 3.2 mg/m2 IV over 60 minutes once on day 1
Supportive therapy
- "All patients received antiemetic prophylaxis."
21-day cycles
References
- PM1183-B-005-14: Trigo J, Subbiah V, Besse B, Moreno V, López R, Sala MA, Peters S, Ponce S, Fernández C, Alfaro V, Gómez J, Kahatt C, Zeaiter A, Zaman K, Boni V, Arrondeau J, Martínez M, Delord JP, Awada A, Kristeleit R, Olmedo ME, Wannesson L, Valdivia J, Rubio MJ, Anton A, Sarantopoulos J, Chawla SP, Mosquera-Martinez J, D'Arcangelo M, Santoro A, Villalobos VM, Sands J, Paz-Ares L. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020 May;21(5):645-654. link to original article contains dosing details in manuscript Epub 2020 Mar 27. PubMed https://clinicaltrials.gov/ct2/show/NCT02454972
Relapsed or refractory disease, subsequent lines
This section includes studies that do not specify an exact line or have yet to be categorized.
Bendamustine monotherapy
Regimen
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Lammers et al. 2014 (VICC THO 0920) | 2009-2012 | Phase 2 | ORR: 33% (95% CI, 14-52%) |
References
- VICC THO 0920: 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 original article link to PMC article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00984542
CAV
CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine
Regimen variant #1, no capping
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Aix et al. 2022 (ATLANTIS) | 2016-2018 | Phase 3 (C) | Doxorubicin & Lurbinectedin | Did not meet primary endpoint of OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
21-day cycles
Regimen variant #2, capped
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Pawel et al. 1999 | NR | Phase 3 (C) | Topotecan | Did not meet primary endpoints of ORR/DOR |
Note: 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 therapy
- G-CSF use per physician discretion
21-day cycle for up to 6 cycles beyond maximal response Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion.
Regimen variant #3
Study | Dates of enrollment | Evidence |
---|---|---|
Ihde et al. 1994 | 1983-1991 | Non-randomized part of RCT |
Note: 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 dosing details in manuscript 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 dosing details in manuscript PubMed
- ATLANTIS: Aix SP, Ciuleanu TE, Navarro A, Cousin S, Bonanno L, Smit EF, Chiappori A, Olmedo ME, Horvath I, Grohé C, Farago AF, López-Vilariño JA, Cullell-Young M, Nieto A, Vasco N, Gómez J, Kahatt C, Zeaiter A, Carcereny E, Roubec J, Syrigos K, Lo G, Barneto I, Pope A, Sánchez A, Kattan J, Zarogoulidis K, Waller CF, Bischoff H, Juan-Vidal O, Reinmuth N, Dómine M, Paz-Ares L. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023 Jan;11(1):74-86. Epub 2022 Oct 14. link to original article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT02566993
Cisplatin & Etoposide (EP)
EP: Etoposide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
O'Bryan et al. 1990 (SWOG S8215) | NR | Phase 3 (E-switch-ic) | BTOC | Did not meet efficacy endpoints |
Ettinger et al. 2002 (ECOG E1588) | 1988-1990 | Non-randomized part of phase 3 RCT |
Preceding treatment
- ECOG E1588: CAV versus ifosfamide versus teniposide, with progression
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
- SWOG S8215: O'Bryan RM, Crowley JJ, Kim PN, Epstein RB, Neilan B, Coltman CA Jr, Stuckey WJ, Pazdur R. Comparison of etoposide and cisplatin with bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide for salvage treatment in small cell lung cancer: a Southwest Oncology Group Study. Cancer. 1990 Feb 15;65(4):856-60. link to original article PubMed
- ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; ECOG. 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 dosing details in manuscript PubMed
Docetaxel monotherapy
Regimen
Study | Evidence |
---|---|
Smyth et al. 1994 | Phase 2 |
References
- Smyth JF, Smith IE, Sessa C, Schoffski P, Wanders J, Franklin H, Kaye SB; 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 original article contains dosing details in abstract PubMed
Epirubicin & Ifosfamide
EI: Epirubicin, Ifosfamide
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Jacot et al. 2012 | 1992-2010 | Phase 2 |
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 therapy
- 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
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 dosing details in manuscript PubMed
Etoposide monotherapy
Regimen
Study | Evidence |
---|---|
Einhorn et al. 1990 | Phase 2 |
Johnson et al. 1990 | Phase 2 |
Note: Oral etoposide to be taken on an empty stomach.
References
- Einhorn LH, Pennington K, McClean J; Hoosier Oncology Group. 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 dosing details in manuscript PubMed
Gemcitabine monotherapy
Regimen variant #1, 5 cycles
Study | Evidence |
---|---|
van der Lee et al. 2001 | Phase 2 |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for up to 5 cycles
Regimen variant #2, indefinite
Study | Evidence |
---|---|
Masters et al. 2003 (ECOG E1597) | Phase 2 |
Note: dose escalation was carried out if patients had less than grade 2 toxicity with cycle 1.
Chemotherapy
- Gemcitabine (Gemzar) as follows:
- Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
- Cycle 2 onwards: 1250 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day 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 dosing details in manuscript PubMed
- ECOG E1597: Masters GA, Declerck L, Blanke C, Sandler A, DeVore R, Miller K, Johnson D; ECOG. 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 dosing details in manuscript PubMed
Ifosfamide monotherapy
Regimen
Study | Evidence |
---|---|
Cantwell et al. 1988 | Phase 2 |
Chemotherapy
- Ifosfamide (Ifex) 5000 mg/m2 IV once on day 1
Supportive therapy
- 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 original article contains dosing details in abstract 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
PI: Paclitaxel, Ifosfamide
Regimen
Study | Evidence |
---|---|
Park et al. 2007a | Phase 2 |
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 therapy
- Mesna (Mesnex) 500 mg/m2 IV three times per day on days 1 & 2, given 15 minutes before, 4 hours after, and 8 hours after ifosfamide (total dose per cycle: 3000 mg/m2)
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 dosing details in manuscript PubMed
Irinotecan monotherapy
Regimen variant #1, weekly
Study | Evidence |
---|---|
Masuda et al. 1992 | Phase 2, <20 pts |
Chemotherapy
- Irinotecan (Camptosar) 100 mg/m2 IV over 90 minutes once per day on days 1, 8, 15
Supportive therapy
- No routine prophylaxis against diarrhea, nausea, or vomiting used.
21-day cycles
Regimen variant #2, q3wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Edelman et al. 2022 (DISTINCT) | 2017-NR in abstract | Phase 3 (C) | 1. Irinotecan & Dinutuximab | Did not meet primary endpoint of OS |
2. Topotecan | Not reported |
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 dosing details in manuscript PubMed
- DISTINCT: Edelman MJ, Dvorkin M, Laktionov K, Navarro A, Juan-Vidal O, Kozlov V, Golden G, Jordan O, Deng CQ, Bentsion D, Chouaid C, Dechev H, Dowlati A, Fernández Núñez N, Ivashchuk O, Kiladze I, Kortua T, Leighl N, Luft A, Makharadze T, Min Y, Quantin X; DISTINCT study investigators. Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer. Lung Cancer. 2022 Apr;166:135-142. Epub 2022 Mar 4. link to original article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT03098030
Paclitaxel monotherapy
Regimen variant #1, every 3 weeks
Study | Evidence |
---|---|
Smit et al. 1998 | Phase 2 |
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Supportive therapy
- Dexamethasone (Decadron) 8 mg PO given twice on day 1; 12 and 6 hours prior to paclitaxel
- Clemastine (Tavist) 2 mg IV push once on day 1; 30 minutes prior to paclitaxel
- One of the following H2 blockers:
- Cimetidine (Tagamet) 300 mg IV push once on day 1; 30 minutes prior to paclitaxel
- Ranitidine (Zantac) 50 mg IV push once on day 1; 30 minutes prior to paclitaxel
21-day cycle for up to 5 cycles
Regimen variant #2, weekly paclitaxel
Study | Evidence |
---|---|
Yamamoto et al. 2006 | Phase 2 |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36
Supportive therapy
- Dexamethasone (Decadron) 20 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to paclitaxel
- Ranitidine (Zantac) 50 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to paclitaxel
- Diphenhydramine (Benadryl) 50 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to paclitaxel
- If ANC less than 1000/μL or WBC count less than 2 x 109/L, G-CSF (type not specified) 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. link to original article contains dosing details in manuscript 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 dosing details in manuscript PubMed
Temozolomide monotherapy
Regimen variant #1, 75 mg/m2/d, 21 out of 28 days
Study | Dates of enrollment | Evidence |
---|---|---|
Pietanza et al. 2012 | 2008-2010 | Phase 2 |
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 therapy
- Ondansetron (Zofran) 8 mg PO once per day on days 1 to 21, 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
Regimen variant #2, 200 mg/m2/d, 5 out of 28 days
Study | Evidence |
---|---|
Zauderer et al. 2014 (MSKCC 08-065) | Phase 2 |
Chemotherapy
- Temozolomide (Temodar) 200 mg/m2 PO once per day on days 1 to 5
Supportive therapy
- Ondansetron (Zofran) 8 mg PO once per day on days 1 to 5; 30 minutes prior to temozolomide
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 dosing details in manuscript PubMed
- MSKCC 08-065: 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. link to original article contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT00740636
Topotecan monotherapy
Regimen variant #1, 1 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Goto et al. 2016 (JCOG0605) | 2007-2012 | Phase 3 (C) | Cisplatin, Etoposide, Irinotecan | Inferior OS |
Chemotherapy
- Topotecan (Hycamtin) 1 mg/m2 IV over 30 minutes once per day on days 1 to 5
21-day cycle for 4 cycles
Regimen variant #2, 1.5 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Pawel et al. 1999 | NR | Phase 3 (E-RT-de-esc) | CAV | Did not meet primary endpoints of ORR/DOR |
Eckardt et al. 2007 | 1999-2001 | Phase 3 (C) | Topotecan; oral | Did not meet primary endpoint of ORR |
von Pawel et al. 2014 (ACT-1) | 2007-2010 | Phase 3 (C) | Amrubicin | Did not meet primary endpoint of OS |
Spigel et al. 2021 (CheckMate 331) | 2015-2017 | Phase 3 (C) | Nivolumab | Might have inferior OS |
Aix et al. 2022 (ATLANTIS) | 2016-2018 | Phase 3 (C) | Doxorubicin & Lurbinectedin | Did not meet primary endpoint of OS |
Blackhall et al. 2021 (TAHOE) | 2017-2018 | Phase 3 (C) | Rovalpituzumab tesirine | Superior OS |
Edelman et al. 2022 (DISTINCT) | 2017-NR in abstract | Phase 3 (C) | 1. Irinotecan & Dinutuximab | Did not meet primary endpoint of OS |
2. Irinotecan | Not reported |
Chemotherapy
- Topotecan (Hycamtin) 1.5 mg/m2 IV over 30 minutes once per day on days 1 to 5
Supportive therapy
- (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 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.
Regimen variant #3, oral route
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Eckardt et al. 2007 | 1999-2001 | Phase 3 (E-switch-ic) | Topotecan; IV (1.5 mg/m2) | Did not meet primary endpoint of ORR |
O'Brien et al. 2006 (GSK 104864/478) | 2000-2004 | Phase 3 (E-esc) | Best supportive care | Seems to have superior OS |
Baize et al. 2020 (GFPC 01-2013) | 2013-2018 | Phase 3 (C) | Carboplatin & Etoposide | Inferior PFS |
Spigel et al. 2021 (CheckMate 331) | 2015-2017 | Phase 3 (C) | Nivolumab | Might have inferior OS |
Note: Duration of treatment details vary depending on reference. In GSK 104864/478, 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. Patients enrolled in GFPC 01-2013 received 6 cycles.
Chemotherapy
- Topotecan (Hycamtin) 2.3 mg/m2 PO once per day on days 1 to 5
21-day cycle for 4 or more cycles (see note)
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 dosing details in manuscript PubMed
- GSK 104864/478: 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00276276
- 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 dosing details in manuscript PubMed
- ACT-1: 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 dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00547651
- JCOG0605: 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; JCOG. 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 dosing details in abstract PubMed UMIN000000828
- GFPC 01-2013: Baize N, Monnet I, Greillier L, Geier M, Lena H, Janicot H, Vergnenegre A, Crequit J, Lamy R, Auliac JB, Letreut J, Le Caer H, Gervais R, Dansin E, Madroszyk A, Renault PA, Le Garff G, Falchero L, Berard H, Schott R, Saulnier P, Chouaid C; Groupe Français de Pneumo-Cancérologie. Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1224-1233. link to original article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT02738346
- CheckMate 331: Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, Audigier-Valette C, Pardo Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331. Ann Oncol. 2021 May;32(5):631-641. Epub 2021 Feb 1. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT02481830
- TAHOE: Blackhall F, Jao K, Greillier L, Cho BC, Penkov K, Reguart N, Majem M, Nackaerts K, Syrigos K, Hansen K, Schuette W, Cetnar J, Cappuzzo F, Okamoto I, Erman M, Langer SW, Kato T, Groen H, Sun Z, Luo Y, Tanwani P, Caffrey L, Komarnitsky P, Reinmuth N. Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study. J Thorac Oncol. 2021 Sep;16(9):1547-1558. Epub 2021 Feb 16. link to original article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT03061812
- DISTINCT: Edelman MJ, Dvorkin M, Laktionov K, Navarro A, Juan-Vidal O, Kozlov V, Golden G, Jordan O, Deng CQ, Bentsion D, Chouaid C, Dechev H, Dowlati A, Fernández Núñez N, Ivashchuk O, Kiladze I, Kortua T, Leighl N, Luft A, Makharadze T, Min Y, Quantin X; DISTINCT study investigators. Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer. Lung Cancer. 2022 Apr;166:135-142. Epub 2022 Mar 4. link to original article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT03098030
- ATLANTIS: Aix SP, Ciuleanu TE, Navarro A, Cousin S, Bonanno L, Smit EF, Chiappori A, Olmedo ME, Horvath I, Grohé C, Farago AF, López-Vilariño JA, Cullell-Young M, Nieto A, Vasco N, Gómez J, Kahatt C, Zeaiter A, Carcereny E, Roubec J, Syrigos K, Lo G, Barneto I, Pope A, Sánchez A, Kattan J, Zarogoulidis K, Waller CF, Bischoff H, Juan-Vidal O, Reinmuth N, Dómine M, Paz-Ares L. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023 Jan;11(1):74-86. Epub 2022 Oct 14. link to original article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT02566993
Vinorelbine monotherapy
Regimen variant #1, 25 mg/m2
Study | Evidence |
---|---|
Furuse et al. 1996a | Phase 2 |
Regimen variant #2, 30 mg/m2
Study | Dates of enrollment | Evidence |
---|---|---|
Jassem et al. 1993 | NR in abstract | Phase 2 |
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 dosing details in abstract 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 dosing details in abstract PubMed