High-dose doxorubicin: an exploration of the dose-response curve in human neoplasia.
Twenty-seven patients with advanced solid tumors (ten with lung cancer, eight with sarcoma, five with melanoma, four with miscellaneous tumors) were treated with high-dose doxorubicin (120 mg/m2) every 3 weeks for a total of 75 courses. As expected, marked myelosuppression was observed, with all patients having a granulocyte count nadir of less than 500 cells/mm3. The median platelet count nadir was 91 X 10(3)/mm3 following the first cycle and 50 X 10(3)/mm3 following the fourth cycle. Moderate or severe stomatitis was seen with 65% of the courses, and 46% of the courses were complicated by fever greater than 101 degrees F. Congestive heart failure was observed in only one patient after five cycles (600 mg/m2) of high-dose therapy. This patient has received 540 mg/m2 of doxorubicin 2 years previously. Radionuclide ventriculography (MUGA) performed serially in 12 patients (eight of whom received 480 mg/m2) and clinical evaluation did not suggest an increased risk of cardiotoxicity at this dose rate. Overall, 11 of 24 (46%) evaluable patients responded (58% if patients with malignant melanoma are excluded). Responses included one complete and three partial responses in eight evaluable patients with lung cancer, one complete and two partial responses in seven evaluable patients with sarcoma, and no objective responses in five patients with malignant melanoma. With appropriate supportive care, repetitive courses of doxorubicin at a dose of 120 mg/m2 can be given to patients of good performance status without a major increase in cardiotoxicity. However, the low complete remission rate, considering the observed toxicity, does not justify routine use of this regimen in patients with solid tumors.
D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D001859:Bone Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006321:Heart / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy; D013280:Stomatitis / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced
D004317:Doxorubicin