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Cyclosporin enhancement of cisplatin chemotherapy in patients with refractory gynecologic cancer. A gynecologic oncology group study
Author(s) -
Manetta Alberto,
Boyle Julie,
Berman Michael L.,
Disaia Philip J.,
Lentz Samuel,
Liao Shu Yuan,
Mutch David,
Slater Lewis
Publication year - 1994
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19940101)73:1<196::aid-cncr2820730134>3.0.co;2-f
Subject(s) - medicine , cisplatin , nephrotoxicity , gynecologic oncology , chemotherapy , refractory (planetary science) , urology , toxicity , oncology , gastroenterology , physics , astrobiology
Background. Cyclosporin has been demonstrated to reverse resistance to several antineoplastic agents including cisplatin in vitro. The purpose of this Phase I trial was to study the potential clinical application of cyclosporin modulation of cisplatin and to establish a tolerable dose of cyclosporin when combined with a standard dose of cisplatin of 75 mg/m 2 . Methods. A course of therapy consisted of two cyclosporin infusions over 2 hours each, 24 hours apart, with cisplatin given 6 hours after the first dose. Treatment was repeated every 21 days. Cyclosporin was studied in a Phase I fashion at five different levels, from 1–5 mg/kg per dose. Twenty patients with refractory gynecologic cancer received 81 courses of therapy. All patients had received extensive prior chemotherapy containing cisplatin. Results. Grade 4 nephrotoxicity was seen in 4 of 20 patients: 1 treated at 1 mg/kg, 1 at 2 mg/kg, and 2 at 5 mg/kg of cyclosporin. The patient treated at the 1 mg/kg level was a partial clinical responder and tolerated six courses. The patient at the 2 mg/kg level had received 14 prior courses of cisplatin and tolerated only two additional courses before a Grade 4 renal toxicity developed. Grade 4 nephrotoxicity developed in the two patients receiving 5 mg after two courses of chemotherapy. Two of the 20 patients achieved a complete response (CR) and 3 patients achieved a partial response (PR), for a total response rate of 25% (5 of 20). The two women who achieved CR started treatment with symptomatic ascites; one of whom also had multiple pulmonary lesions that were no longer evident after three courses of therapy. Conclusions. Cyclosporin at a dose of 4 mg/kg per day given for 2 consecutive days in association with 75 mg/m 2 of cisplatin can be given with reasonable assurance of safety.