Dose intensification of cisplatin chemotherapy through biweekly administration.
OBJECTIVE
Dose intensity (DI, expressed in mg/m2/wk) may be an important factor in the clinical use of cisplatin (DDP). We have explored the shortening of the cycle interval as a way to increase the DI of DDP.


METHODS
DDP 180 mg/m2 was given intravenously (i.v.) over 4 hours; sodium thiosulfate (STS) was given i.v. in the opposite arm at a loading dose of 4 g/m2, followed by 12 g/m2 over 6 hours. Each cycle was repeated every two weeks. Seventy-five cycles were administered to 28 patients in this clinical trial.


RESULTS
In 19 patients who received 2 or more cycles of chemotherapy, a delay of three or more days was required on 17/66 courses (26%); the mean DDP DI actually received by these patients was 83 mg/m2/wk (88% of the planned DI). The major side effect was ototoxicity; this occurred in 9 patients (33%), but none required a hearing aid. Myelosuppression was moderate with thrombocytopenia greater than neutropenia. Nephrotoxicity (creatinine > 2 mg/dl) occurred on only 2 cycles (3%). Three patients (11%) developed symptoms of peripheral neuropathy. In 23 evaluable patients, the overall response rate was 39%.


CONCLUSIONS
It is feasible to give 180 mg/m2 of DDP and STS every two weeks with tolerable nephrotoxicity but without blocking other types of toxicity, such as myelosuppression and ototoxicity. The shortening of cycle intervals resulted in a markedly increased DI.
Kim
S
S
Department of Medicine, University of California, San Diego, La Jolla.
Howell
S B
SB
McClay
E
E
Kirmani
S
S
Goel
R
R
Plaxe
S
S
Braly
P
P
Bonetti
A
A
D000328:Adult; D000368:Aged; D001855:Bone Marrow Diseases / Q000139:chemically induced; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000037:antagonists & inhibitors; D004334:Drug Administration Schedule; D005260:Female; D006311:Hearing Disorders / Q000139:chemically induced; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D013885:Thiosulfates / Q000008:administration & dosage*
D013885:Thiosulfates; C017717:sodium thiosulfate; D002945:Cisplatin