Preliminary pharmacologic and clinical evaluation of camptothecin sodium (NSC-100880)
Gottlieb, J.A.; Guarino, A.M.; Call, J.B.; Oliverio, V.T.; Block, J.B.
Cancer ChemoTherapy Reports 54(6): 461-470
1970
ISSN/ISBN: 0069-0112 PMID: 4946015 Document Number: 5643
Camptothecin sodium, a novel alkaloid with heterocyclic ring structure extracted from the oriental tree Camptotheca acuminata, was given to 18 adults during a dose-establishing clinical trial. Sixteen patients with various advanced solid tumors received 35 single intravenous injections of 0.5-40.0 mg of camptothecin per kilogram of body weight at intervals of 2-4 weeks. Two additional patients, one with angiosarcoma and one with acute myelogenous leukemia, received 5 injections of 2 or 2.5 mg/kg at intervals of 3 days. Partial remissions (>50% mass decreases) were noted in 5 patients, and evidence of objective response was noted in 6 others. Responses occurred predominantly in patients with advanced and often refractory gastrointestinal carcinoma. Although response durations were brief at the dosage schedules used (median=2 +mos), they were useful to the patients, as they were accompanied in some by improvement in nutritional and performance status. Toxicity was generally tolerable and consisted predominantly of alopecia, mild gastrointestinal symptoms, hemorrhagic cystitis, and dose-limiting myelosuppression. A dosage schedule of 5 or 7.5 mg/kg, given every 2 weeks, was well tolerated in patients with adequate renal function. Pharmacologic studies revealed that a high percent of drug is bound to plasma proteins after intravenous administration, with drug detectable in the plasma up to 6 days later. A mean of 17.4% of unmetabolized drug was found in the first 48 hours' urine collection. No fluorescent urinary metabolites were found and no drug was detected in multiple analyses of various body organs or in the tumor itself.
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