Phase II study of sequential topoisomerase (Top) targeting regimens (reg) with irinotecan/oxaliplatin (I/O) followed by etoposide/carboplatin (E/Crb) in patients with extensive small cell lung cancer (SCLC)

Abstract

19095 Background: Top inhibitors are active agents in SCLC, and preclinical models indicate that sequential administration of Top I and Top II targeting drugs can result in additive or synergistic antitumor activity. Methods: The primary objective of this study is to determine the objective response (OR) rate of sequential I/O (Regimen A) followed by E/Crb (Regimen B). Secondary endpoints include toxicities (Tx), time to progression (TTP), overall survival (OS), and immunohistochemical (IHC) evaluation of Top I/II and excision repair cross complementation I (ERCC-I) expression in tumor specimens. Chemotherapy naïve patients receive 5 cycles of sequential therapy of reg A→B. Each cycle consists of I (150–200 mg/m2) and O (85mg/m2) on day 1 followed by Crb (AUC = 6) on day 15 and E (100mg /m2) on days 15, 16, and 17. Pegfilgastrim (6mg) is given on days 2 and 18 of each 28 day cycle. Response assessment is performed after every 2 cycles. Primary refractory or relapsed patients are treated with reg A only. Results: Demographic characteristics of the 26 enrolled patients are: median age 62; gender ratio 13/13 (male/female); 10 with performance status 0–1; and 3 have primary refractory disease upon enrollment. Four patients are not included in the response data, 3 are too early to evaluate and 1 was evaluable for Tx only. Data from chemotherapy naïve patients with > 2 cycles of treatment (n=16) indicate 1 complete response, 13 partial responses, and 2 with stable disease. The median TTP is 7.5 months in the 6 patients with progression. No OR are observed in previously refractory patients (n=3). Grade 3 and 4 Tx in the 1st cycle of regimen A are neutropenia (ANC) (n=3) and fatigue (n=13). Reg B Tx are anemia (HGB) (n=5), ANC (n=5), thrombocytopenia (PLT) (n=16), and fatigue (n=4). The most common overall Tx in reg A are mild to moderate nausea and vomiting and HGB. The main dose limiting Tx (DLT) is grade 4 PLT in reg B. Conclusions: Early data indicates that this sequential approach may enhance the efficacy of chemotherapy in newly diagnosed SCLC patients. This study is actively enrolling patients, and updated findings including efficacy and pharmacogenomic correlations will be presented. No significant financial relationships to disclose.