Amifostine (AMI) selectively protects against cumulative toxicities of cyclophosphamide (C) and cisplatin (P)

Two hundred and forty-two advanced ovarian cancer pts were randomized to receive 6 cycles of 1 gm/m 2 C and 100 mg/m 2 P ± 910 mg/m 2 Ami every 3 weeks. Ami significantly reduced the incidence of cumulative nephrotoxicity. Protracted elevations of serum creatinine were reduced from 13.3% with CP to 1.6%, with Ami + CP, P = 0.001. Following the last cycle of chemotherapy, 32% CP patients vs 10% Ami + CP had ≥40% decrease in creatinine clearance, P P = 0.001). Additionally, 7% of CP patients compared to 1% of Ami + CP discontinued therapy due to hematologic toxicity, P = 0.016. Fever and, or infection associated with grade 4 neutropenia was reduced by 52% (21% to 10%) in the Ami + CP arm, P = 0.019 with a consequent 60% reduction in days in hospital, P = 0.019 and days on antibiotics, P = 0.031. The incidence of grade 4 neutropenia was also significantly reduced in the Ami + CP arm at the last cycle, P = 0.001. Antitumor efficacy as assessed by pathologic tumor response rates and survival was preserved. With a median follow-up of 41 months, survival curves are identical; median survivals: 31 months. Ami selectively protects normal tissues from the hematologic and nonhematologic toxicities from CP without any loss of antitumor actIvity.