Randomized phase II study (EORTC 08062) of amrubicin as single agent or in combination with cisplatin versus etoposidecisplatin as first-line treatment in patients (pts) with extensive disease small cell lung cancer (ED SCLC)

Background: Outcome for pts with ED SCLC remains poor, despite standard treatment with platinum and etoposide (E). Amrubicin (A) is a synthetic anthracycline and a potent topoisomerase II inhibitor, with less cardiotoxicity than doxorubicin, approved in Japan for the treatment of NSCLC and SCLC. Methods: Eligible pts had previously untreated, histologically confirmed ED SCLC,WHO performance status (PS) 0-2and measurable disease according to RECIST. Pts were randomized to 3 weekly cycles of either (1) A alone 45 mg/m2 d1-3, (2) cisplatin (C) 60 mg/m2 d1 and A 40 mg/m2 d1-3 or (3) E 100 mg/ m2 d1, d2-3 i.v/po and C 75 mg/m2 d1. The primary endpoint was overall response rate (ORR) aiming at ORR = 80% and powered to rule out an ORR < 55% in any experimental arm. Patients were stratified by center, gender and PS. To declare success, 19 responses out of 27 eligible pts who started treatment (ORR of at least 70%) were needed in each arm using a Fleming design. Results: The number of randomized/eligible pts who started treatment was 33/28 in Arm 1, 33/30 in arm 2 and 33/30 in arm 3, respectively. Major patient characteristics including age, sex and PS were well balanced between the arms. The median number of chemotherapy cycles received was 5, 6 and 6. Primary prophylaxis with pegfilgrastim was added in the later part of the trial in arms 1-3 (57%, 43%, 37%); grade (G) 3-4 hematological toxicity in arms 1-3 was neutropenia (73%, 73%, 69%); thrombocytopenia (17%, 15%, 9.4%), anemia (10%, 15%, 3.1%) and febrile neutropenia (17%,15%,14%). Early deaths including treatment related were 1, 3 and 3 pts respectively. Cardiac toxicity did not differ among the 3 arms. Out of 88 eligible pts who started treatment, the response rate assessed by investigators was 17 (61%), 23 (77%) and 19 (63%) for arm 1, 2 and 3, respectively. Conclusions: A + C was associated with the highest response rate and further evaluation of this combination is warranted. Independent central review is still on-going.