1058 A phase II evaluation of bone marrow protection by ethyol®(Amifostine)(Am) in patients with non-small cell lung cancer (NSCLC) treated with carboplatin(c)

Amifostine(Am), provided by US Bioscience, is a thiol compound which has been shown to protect normal tissues from alkylating agents without loss of anti-tumour activity. 21 patients (pts) with inoperable NSCLC were entered into a randomised phase II study to determine the extent and duration of bone marrow protection by Am and provide a preliminary indication of whether the given dose intensity of carboplatin(C) with Am (CAm-arm) produces a higher than expected therapeutic benefit. 2 pts had an ECOG=0, 12 pts had ECOG=1 and 6 pts had ECOG=2. Median age for CAm-arm=64 (Range 45–69), C alone (C-arm)=61 (Range 41–70). All pts received C 600mg/m2before being randomized to receive either 3 cycles of C or CAm at 28 day intervals. Originally pts received 3 infusions of Am 910mg/m2at each cycle, but this was reduced to 683mg/m2because of toxicities. All pts were evaluable for toxicity and 18 pts were evaluable for response. 21 courses of CA-arm were compared with 25 courses of C-arm. Time to platelet recovery (100 × 109/l) (13.5 vs 21 days; P=0.04) and need for iv antibiotics and hospitalisation were reduced in the CAm-arm (3% vs 23%; P=0.03). Tumour response rates for CAm-arm (5/9 pts had PRs) and C-arm (2/9 had PRs) were 56% (95% CI=21–86)and 22% (95% CI=3–60), respectively. Median survival time for CAm-arm was 14 months and for C-arm was 9 months, suggesting that the combined modality i.e. CAm-arm might enhance the cytotoxic activity of C as has been suggested in mice (Treskes (1994) Eur. J. Cancer.30a, 183–187). Main toxicities of Am are hypotension, flushing, nausea and vomiting, sneezing and dizziness. In conclusion, these results show that Am given with C reduces the duration of thrombocytopenia and may provide protection from severe infection and reduce the duration of hospitalisation. Further studies from this combination are warranted.