Phase I clinical study of heptaplatin (H) and paclitaxel (P) in previously treated patients with advanced solid tumor

Abstract

2122 Background: Heptaplatin is a recently developed platinum analogue which has been reported to be less toxic than cisplatin. In a phase I clinical trial, the maximum tolerated dose (MTD) was 480 mg/m2 once every 4 weeks with dose limiting toxicity (DLT) of myelosuppression and hepatotoxicity (Proc ASCO; 14:A1556 1995). But, randomized study showed H 400 mg/m2 was more nephrotoxic than cisplatin 60 mg/m2 in terms of azotemia and proteinuria when combined with 5-FU (Ahn JH et al. Cancer Chemother Pharmacol. 2002). We initiated a phase I study of H plus P to determine MTD, DLT and toxicities, especially nephrotoxicity. Methods: Eligible pts were those with advanced solid tumor, age 20–65, ECOG 0–1, adequate organ function, 1 or more prior chemotherapy except platinum or taxane and informed consent. P was given first over 60 minutes with fixed dose of 60 mg/m2 followed by H over 60 minutes on days 1, 8 and 15, every 4 weeks. The dose escalation of H was designed to treat cohorts of 3 pts at doses of 120, 150, 200, 250, 300 mg/m2. DLT and MTD pertained to cycle 1 only. Serial blood samples were collected for determination of H and P pharmacokinetics (PK). Results: Between 2002/10 and 2003/12, 15 pts were entered into the study and all pts were evaluated for toxicity and response; median age: 45 (33–65)years, M/F: 9/6; Tumor types: 7 non-small cell lung cancers, 6 colorectals, 1 breast, and 1 gastric cancer. Neither DLT nor nephrotoxicity has occurred. The highest toxicity grade was 3 and no grade 4 toxicity; 4 neutropenia, 1 anorexia, 1 dyspnea, and 1 constipation. Antitumor acitivty has been observed with 3 PR (2 NSCLC, 1 Breast). Conclusions: This weekly combination regimen showed interesting response rate with good tolerability. MTD has not been defined and dose escalation continues. The PK data will be presented. No significant financial relationships to disclose.