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Cisplatin, irinotecan, and bevacizumab for untreated extensive-stage small-cell lung cancer: CALGB 30306, a phase II study.

ABSTRACT: The efficacy of cisplatin, irinotecan, and bevacizumab was evaluated in patients with extensive-stage small-cell lung cancer (ES-SCLC).Patients with ES-SCLC received cisplatin 30 mg/m(2) and irinotecan 65 mg/m(2) on days 1 and 8 plus bevacizumab 15 mg/kg on day 1 every 21 days for six cycles on this phase II study. The primary end point was to differentiate between 50% and 65% 12-month survival rates.Seventy-two patients were enrolled between March 2005 and April 2006; four patients canceled, and four were ineligible. Grade 3 or 4 toxicities included neutropenia (25%), all electrolyte (23%), diarrhea (16%), thrombocytopenia (10%), fatigue (10%), nausea (10%), hypertension (9%), anemia (9%), infection (7%), vascular access thrombosis (2%), stroke (2%), and bowel perforation (1%). Three deaths (5%) occurred on therapy as a result of pneumonitis (n = 1), stroke (n =1), and heart failure (n = 1). Complete response, partial response, and stable disease occurred in three (5%), 45 (70%), and 11 patients (17%), respectively. Progressive disease occurred in one patient (2%). Overall response rate was 75%. Median progression-free survival (PFS) was 7.0 months (95% CI, 6.4 to 8.4 months). Median overall survival (OS) was 11.6 months (95% CI, 10.5 to 15.1 months). Hypertension ? grade 1 was associated with improved OS after adjusting for performance status (PS) and age (hazard ratio [HR], 0.55; 95% CI, 0.31 to 0.97; P = .04). Lower vascular endothelial growth factor levels correlated with worse PFS after adjusting for age and PS (HR, 0.90; 95% CI, 0.83 to 0.99; P = .03).PFS and OS times were higher compared with US trials in ES-SCLC with the same chemotherapy. However, the primary end point of the trial was not met. Hypertension was associated with improved survival after adjusting for age and PS.

SUBMITTER: Ready NE

PROVIDER: S-EPMC3221525 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Cisplatin, irinotecan, and bevacizumab for untreated extensive-stage small-cell lung cancer: CALGB 30306, a phase II study.

Ready Neal E NE Dudek Arkadiusz Z AZ Pang Herbert H HH Hodgson Lydia D LD Graziano Stephen L SL Green Mark R MR Vokes Everett E EE

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20111003 33

<h4>Purpose</h4>The efficacy of cisplatin, irinotecan, and bevacizumab was evaluated in patients with extensive-stage small-cell lung cancer (ES-SCLC).<h4>Patients and methods</h4>Patients with ES-SCLC received cisplatin 30 mg/m(2) and irinotecan 65 mg/m(2) on days 1 and 8 plus bevacizumab 15 mg/kg on day 1 every 21 days for six cycles on this phase II study. The primary end point was to differentiate between 50% and 65% 12-month survival rates.<h4>Results</h4>Seventy-two patients were enrolled ...[more]

PMID: 21969504

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Project description:PurposeTo evaluate the efficacy of maintenance sunitinib after chemotherapy for small-cell lung cancer (SCLC).Patients and methodsThe Cancer and Leukemia Group B 30504 trial was a randomized, placebo-controlled, phase II study that enrolled patients before chemotherapy (cisplatin 80 mg/m(2) or carboplatin area under the curve of 5 on day 1 plus etoposide 100 mg/m(2) per day on days 1 to 3 every 21 days for four to six cycles). Patients without progression were randomly assigned 1:1 to placebo or sunitinib 37.5 mg per day until progression. Cross-over after progression was allowed. The primary end point was progression-free survival (PFS) from random assignment for maintenance placebo versus sunitinib using a one-sided log-rank test with α = .15; 80 randomly assigned patients provided 89% power to detect a hazard ratio (HR) of 1.67.ResultsOne hundred forty-four patients were enrolled; 138 patients received chemotherapy. Ninety-five patients were randomly assigned; 10 patients did not receive maintenance therapy (five on each arm). Eighty-five patients received maintenance therapy (placebo, n = 41; sunitinib, n = 44). Grade 3 adverse events with more than 5% incidence were fatigue (19%), decreased neutrophils (14%), decreased leukocytes (7%), and decreased platelets (7%) for sunitinib and fatigue (10%) for placebo; grade 4 adverse events were GI hemorrhage (n = 1) and pancreatitis, hypocalcemia, and elevated lipase (n = 1; all in same patient) for sunitinib and thrombocytopenia (n = 1) and hypernatremia (n = 1) for placebo. Median PFS on maintenance was 2.1 months for placebo and 3.7 months for sunitinib (HR, 1.62; 70% CI, 1.27 to 2.08; 95% CI, 1.02 to 2.60; one-sided P = .02). Median overall survival from random assignment was 6.9 months for placebo and 9.0 months for sunitinib (HR, 1.28; 95% CI, 0.79 to 2.10; one-sided P = .16). Three sunitinib and no placebo patients achieved complete response during maintenance. Ten (77%) of 13 patients evaluable after cross-over had stable disease on sunitinib (6 to 27 weeks).ConclusionMaintenance sunitinib was safe and improved PFS in extensive-stage SCLC.

Project description:BackgroundNo novel chemotherapeutic combinations have demonstrated superior efficacy to etoposide/cisplatin (EP), a standard treatment regimen for extensive-stage small cell lung carcinoma (ES-SCLC) over the past decade. We aimed to compare the efficacy and safety of belotecan/cisplatin (BP) and EP regimens in chemotherapy- and radiotherapy-naïve patients with previously untreated ES-SCLC.MethodsWe conducted a multi-center, randomized, open-label, parallel-group, phase III clinical study. A total of 157 patients were recruited at 14 centers with 147 patients meeting the inclusion/exclusion criteria and randomized to either BP (n = 71) or EP (n = 76) treatment arms. A non-inferior response rate (RR) in the BP arm, analyzed by intent-to-treat analysis according to Response Evaluation Criteria in Solid Tumors version 1.0 criteria, was used as the primary endpoint. The secondary endpoints were progression-free survival (PFS) and overall survival (OS).ResultsIn the BP arm, one patient had a complete response, 41 had a partial response (PR), and 17 had stable disease (SD). In the EP arm, 35 patients had PR and 28 had SD. The RR in the BP arm was non-inferior to the EP regimen in patients with ES-SCLC (BP: 59.2 %, EP: 46.1 %, difference: 13.1 %, 90 % two-sided confidence interval: -0.3-26.5, meeting the predefined non-inferiority criterion of -15.0 %). No significant differences in OS or PFS were observed between the treatment arms. Hematologic toxicities, including grade 3/4 anemia and thrombocytopenia, were significantly more prevalent in the BP arm than the EP arm.ConclusionsThe RR to the BP regimen was non-inferior to the EP regimen in chemotherapy- and radiotherapy-naïve patients with previously untreated ES-SCLC. Hematologic toxicities were significantly more prevalent in the BP group, indicating that BP should be used with care, particularly in patients with a poor performance status. Further studies assessing PFS and OS are required to validate the superiority of the BP regimen.Trial registrationClinicalTrials.gov identifier NCT00826644 . Date of Registration: January 21, 2009.

Project description:PURPOSE:Veliparib, a poly (ADP ribose) polymerase inhibitor, potentiated standard chemotherapy against small-cell lung cancer (SCLC) in preclinical studies. We evaluated the combination of veliparib with cisplatin and etoposide (CE; CE+V) doublet in untreated, extensive-stage SCLC (ES-SCLC). MATERIALS AND METHODS:Patients with ES-SCLC, stratified by sex and serum lactate dehydrogenase levels, were randomly assigned to receive four 3-week cycles of CE (75 mg/m2 intravenously on day 1 and 100 mg/m2 on days 1 through 3) along with veliparib (100 mg orally twice per day on days 1 through 7) or placebo (CE+P). The primary end point was progression-free survival (PFS). Using an overall one-sided 0.10-level log-rank test, the study had 88% power to demonstrate a 37.5% reduction in the PFS hazard rate. RESULTS:A total of 128 eligible patients received treatment on protocol. The median age was 66 years, 52% of patients were men, and Eastern Cooperative Oncology Group performance status was 0 for 29% of patients and 1 for 71%. The respective median PFS for the CE+V arm versus the CE+P arm was 6.1 versus 5.5 months (unstratified hazard ratio [HR], 0.75 [one-sided P = .06]; stratified HR, 0.63 [one-sided P = .01]), favoring CE+V. The median overall survival was 10.3 versus 8.9 months (stratified HR, 0.83; 80% CI, 0.64 to 1.07; one-sided P = .17) for the CE+V and CE+P arms, respectively. The overall response rate was 71.9% versus 65.6% (two-sided P = .57) for CE+V and CE+P, respectively. There was a significant treatment-by-strata interaction in PFS: Male patients with high lactate dehydrogenase levels derived significant benefit (PFS HR, 0.34; 80% CI, 0.22 to 0.51) but there was no evidence of benefit among patients in other strata (PFS HR, 0.81; 80% CI, 0.60 to 1.09). The following grade ? 3 hematology toxicities were more frequent in the CE+V arm than the CE+P arm: CD4 lymphopenia (8% v 0%; P = .06) and neutropenia (49% v 32%; P = .08), but treatment delivery was comparable. CONCLUSION:The addition of veliparib to frontline chemotherapy showed signal of efficacy in patients with ES-SCLC and the study met its prespecified end point.

Dataset Information

Cisplatin, irinotecan, and bevacizumab for untreated extensive-stage small-cell lung cancer: CALGB 30306, a phase II study.

Publications

Cisplatin, irinotecan, and bevacizumab for untreated extensive-stage small-cell lung cancer: CALGB 30306, a phase II study.

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