BACKGROUND: We attempted to determine the maximum tolerated dose and toxicity of etoposide (VP-16) when administered in combination with carboplatin (CBDCA) (300 mg m-2) and administered via the intraperitoneal (IP) route. METHODS AND MATERIALS: A total of 26 patients were treated on this trial. CBDCA was administered at a fixed dose of 300 mg m-2) while VP-16 was started at a dose of 200 mg m-2 and escalated at 50 mg m-2 increments. Both agents were mixed together in 2 litres of 5% Dextrose and administered as quickly as possible into the peritoneal cavity. Pharmacokinetic studies were performed at the maximum tolerated dose (MTD). RESULTS: The MTD for this regimen was CBDCA 300 mg m-2 and VP-16 350 mg m-2. Patients > or = 70 years of age or who had received more than six cycles of previous chemotherapy, tolerated this regimen poorly. The MTD for this group of patients was CBDCA 200 mg m-2 and VP-16 50 mg m-2. Neutropenia was the dose limiting toxicity for both groups. The mean peritoneal/plasma peak ratio was 18.3 for CBDCA and 12.7 for VP-16. The pharmacologic advantage (peritoneal/plasma AUC ratio) was 14.9 for CBDCA and 8.8 for VP-16. Although measurable disease was not a requirement for entrance into this study a response rate of 27% was noted in 15 patients with evaluable disease who had ovarian cancer. CONCLUSIONS: A pharmacologic advantage exists for both CBDCA and VP-16 when administered together via the IP route.
BACKGROUND: We attempted to determine the maximum tolerated dose and toxicity of etoposide (VP-16) when administered in combination with carboplatin (CBDCA) (300 mg m-2) and administered via the intraperitoneal (IP) route. METHODS AND MATERIALS: A total of 26 patients were treated on this trial. CBDCA was administered at a fixed dose of 300 mg m-2) while VP-16 was started at a dose of 200 mg m-2 and escalated at 50 mg m-2 increments. Both agents were mixed together in 2 litres of 5% Dextrose and administered as quickly as possible into the peritoneal cavity. Pharmacokinetic studies were performed at the maximum tolerated dose (MTD). RESULTS: The MTD for this regimen was CBDCA 300 mg m-2 and VP-16 350 mg m-2. Patients > or = 70 years of age or who had received more than six cycles of previous chemotherapy, tolerated this regimen poorly. The MTD for this group of patients was CBDCA 200 mg m-2 and VP-16 50 mg m-2. Neutropenia was the dose limiting toxicity for both groups. The mean peritoneal/plasma peak ratio was 18.3 for CBDCA and 12.7 for VP-16. The pharmacologic advantage (peritoneal/plasma AUC ratio) was 14.9 for CBDCA and 8.8 for VP-16. Although measurable disease was not a requirement for entrance into this study a response rate of 27% was noted in 15 patients with evaluable disease who had ovarian cancer. CONCLUSIONS: A pharmacologic advantage exists for both CBDCA and VP-16 when administered together via the IP route.
Authors: J F Bishop; D Raghavan; R Stuart-Harris; G Morstyn; R Aroney; R Kefford; K Yuen; J Lee; P Gianoutsos; I N Olver Journal: J Clin Oncol Date: 1987-10 Impact factor: 44.544
Authors: H Anderson; J Wagstaff; D Crowther; R Swindell; M J Lind; J McGregor; M S Timms; D Brown; P Palmer Journal: Eur J Cancer Clin Oncol Date: 1988-09
Authors: S Zimm; S M Cleary; W E Lucas; R J Weiss; M Markman; P A Andrews; M A Schiefer; S Kim; C Horton; S B Howell Journal: Cancer Res Date: 1987-03-15 Impact factor: 12.701
Authors: W W ten Bokkel Huinink; M E van der Burg; A T van Oosterom; J P Neijt; M George; J P Guastalla; C H Veenhof; N Rotmensz; O Dalesio; J B Vermorken Journal: Cancer Treat Rev Date: 1988-06 Impact factor: 12.111
Authors: T C Shea; M Flaherty; A Elias; J P Eder; K Antman; C Begg; L Schnipper; E Frei; W D Henner Journal: J Clin Oncol Date: 1989-05 Impact factor: 44.544
Authors: N Colombo; J L Speyer; M Green; R Canetta; U Beller; J C Wernz; M Meyers; T Widman; R H Blum; M Piccart Journal: Cancer Chemother Pharmacol Date: 1989 Impact factor: 3.333