A randomized trial of carboplatin versus iproplatin in untreated advanced ovarian cancer.

Abstract

Between August 1984 and October 1987, 120 patients with stage IC to IV epithelial ovarian cancer were randomly assigned to receive carboplatin (400 mg/m2) or iproplatin (300 mg/m2) every 4 weeks as initial treatment. Stratification was made according to International Federation of Gynecology and Obstetrics (FIGO) stage and according to size of residual disease after surgery. Response was evaluated after six courses when patients were restaged, with laparoscopy or laparotomy in clinical complete responders or those with no assessable disease. Treatment was then stopped in surgically proven complete responders. Patients with partial (PR) or minor response (MR) received a further six courses of their original drug at a reduced dose (carboplatin 300 mg/m2, iproplatin 225 mg/m2). Patients with stable (SD), progressive (PD), or recurrent disease were treated with cyclophosphamide (1 g/m2). The response rates were 63% (95% confidence interval [CI], 50% to 74%) for carboplatin and 38% (95% CI, 26% to 51%) for iproplatin. Fifteen patients were not assessable for response. The median survival was 114 weeks (95% CI, 82 to 233 weeks) for carboplatin patients and 68 weeks (95% CI, 48 to 82 weeks) for iproplatin patients (P = .008). The amount of residual disease after initial laparotomy was a prognostic factor for survival. Myelosuppression was the main toxicity and was greater with iproplatin. This study shows carboplatin to be more active than iproplatin in the treatment of ovarian cancer and less toxic. Few responses to cyclophosphamide occurred following either drug, implying resistance to the alkylating agent.

Conjugation of Cisplatin Analogues and Cyclooxygenase Inhibitors to Overcome Cisplatin Resistance

“…[23] Reduction potentials that are too high lead to reduction in the blood, resulting in severe side effects (e.g., tetraplatin, systemic toxicity), [24] while excessively low potentials result in excretion of the intact compounds (e.g., iproplatin, weak activity). [25] The platinum(IV) conjugates 3 , 4 , 5 , and 6 showed irreversible reduction, resulting in only one peak in the cyclic voltammograms (Figure S2, Supporting Information), which is caused by the loss of the axial ligands and change of the coordination geometry. [9] All conjugates exhibited similar reduction potentials (Table 1) which are similar to those of other reported platinum(IV) carboxylato complexes.…”

Tumour-inhibiting platinum complexes—state of the art and future perspectives

“…Iproplatin (CHIP, JM-9), cis-dichloro-trans-dihydroxybis(isopropylamine)platinum(IV), was extensively studied at the same time as carboplatin and was the first platinum(IV) complex to enter clinical trials, but clearly failed to prove advantageous over carboplatin in terms of response and survival of patients with advanced ovarian cancer in a randomized phase III trial (Trask et al 1991), which eventually led to cessation of its development. Clinical trials of several other compounds failed to confirm the improved toxicological profile expected from previous animal experiments: platinum uracil blue exhibited unpredicted cardiac toxicity; spiroplatin (TNO-6), (1,1-diaminomethylcyclohexane)sulphatoplatinum(II), and JM-40, (ethane-1,2-diamine)malonatoplatinum(II), failed due to renal toxicity.…”

Tuning of lipophilicity and cytotoxic potency by structural variation of anticancer platinum(IV) complexes

“…In the case of tetraplatin, the toxicity was too high [6], whereas iproplatin was found to be not active enough [7]. In this context it has to be mentioned that platinum(IV) compounds act as prodrugs, whereby the biologically more active platinum(II) species is obtained via reduction of its platinum(IV) analog (activation by reduction) [5,8].…”