Carboplatin and Etoposide With or Without Palifosfamide in Untreated Extensive-Stage Small-Cell Lung Cancer: A Multicenter, Adaptive, Randomized Phase III Study (MATISSE).

Purpose To evaluate the efficacy of the addition of palifosfamide to carboplatin and etoposide in extensive stage (ES) small-cell lung cancer (SCLC). Patients and Methods MATISSE was a randomized, open-label, adaptive phase III study. Previously untreated patients with ES SCLC were randomly assigned in a 1:1 fashion to receive carboplatin at area under the serum concentration-time curve 5 on day 1 plus etoposide 100 mg/m2 per day on days 1 to 3 every 21 days (CE) or carboplatin at area under the serum concentration-time curve 4 on day 1 plus etoposide 100 mg/m2 per day plus palifosfamide 130 mg/m2 per day on days 1 to 3 every 21 days (PaCE). The primary end point was overall survival. Results In all, 188 patients were enrolled; 94 patients received CE and 94 patients received PaCE. The median age on both arms was 61 years. Six cycles of chemotherapy were completed on both arms of the study by approximately 50% of the patients. Serious adverse events were documented and did not differ significantly between patients receiving PaCE and those receiving CE. Median overall survival was similar between both arms with 10.03 months on PaCE and 10.37 months on CE ( P = .096). Conclusion The addition of palifosfamide to CE failed to improve survival in ES SCLC.

[1]  L. Paz-Ares,et al.  ATLANTIS: a Phase III study of lurbinectedin/doxorubicin versus topotecan or cyclophosphamide/doxorubicin/vincristine in patients with small-cell lung cancer who have failed one prior platinum-containing line. , 2019, Future oncology.

[2]  Roman K. Thomas,et al.  Genomic and Functional Fidelity of Small Cell Lung Cancer Patient-Derived Xenografts. , 2018, Cancer discovery.

[3]  A. Farago,et al.  Current standards for clinical management of small cell lung cancer. , 2018, Translational lung cancer research.

[4]  R. Rosell,et al.  Unraveling the genomic complexity of small cell lung cancer. , 2016, Translational lung cancer research.

[5]  N. Socci,et al.  Next-Generation Sequencing of Pulmonary Large Cell Neuroendocrine Carcinoma Reveals Small Cell Carcinoma–like and Non–Small Cell Carcinoma–like Subsets , 2016, Clinical Cancer Research.

[6]  F. de Marinis,et al.  Cellular and molecular biology of small cell lung cancer: an overview. , 2016, Translational lung cancer research.

[7]  E. Vokes,et al.  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). , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  M. von Mehren,et al.  New drugs and combinations for the treatment of soft-tissue sarcoma: a review , 2012, Cancer management and research.

[9]  R. Gorlick,et al.  Preclinical activity of palifosfamide lysine (ZIO-201) in pediatric sarcomas including oxazaphosphorine-resistant osteosarcoma , 2009, Cancer Chemotherapy and Pharmacology.

[10]  S. Sleijfer,et al.  The pharmacologic basis of ifosfamide use in adult patients with advanced soft tissue sarcomas. , 2007, The oncologist.

[11]  Michael,et al.  Small cell lung cancer: have we made any progress over the last 25 years? , 2007, The oncologist.

[12]  K. Mori,et al.  Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. , 2002, The New England journal of medicine.

[13]  L. Einhorn,et al.  Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  D. Ettinger,et al.  Phase II study of paclitaxel in patients with extensive-disease small-cell lung cancer: an Eastern Cooperative Oncology Group study. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  T. Corbett,et al.  Isophosphoramide mustard, a metabolite of ifosfamide with activity against murine tumours comparable to cyclophosphamide. , 1983, British Journal of Cancer.

[16]  M. P. Gamcsik,et al.  Mechanisms of resistance against cyclophosphamide and ifosfamide: can they be overcome without sacrificing selectivity? , 2002, Cancer treatment and research.

[17]  G. Giaccone,et al.  Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes? , 2022 .