This study addressed two major questions regarding therapeutic use of Adriamycin ([Adr] Adria Laboratories, Columbus, OH) in adult soft tissue sarcomas: the influence of dosing schedule and the value of adding imidazole carboxamide (DTIC) to Adr. Patients with objectively measurable metastatic soft tissue sarcomas were randomized to Adr 70 mg/m2 intravenously (IV) day 1 and every 3 weeks (94 patients); Adr 20 mg/m2 IV day 1, 2, and 3, and 15 mg/m2 IV day 8 and weekly thereafter (89 patients); and Adr 60 mg/m2 IV day 1 and DTIC 250 mg/m2 days 1 to 5, repeated every 3 weeks (92 patients). The regimens using Adr as a single agent resulted in an equivalent response frequency (18% and 16%) and survival (median, 8.0 and 8.4 months). DTIC significantly increased (P less than .02) the overall response frequency of Adr to 30%. However, DTIC did not influence survival (median, 8.0 months) or increase the number of complete responses. The toxicities of the two single-agent regimens differed: Adr weekly resulted in more stomatitis (P = .09) and less hematologic toxicity (P less than .05). DTIC resulted in substantially increased toxicity, primarily gastrointestinal (P less than .002); overall, 98% of patients receiving Adr-DTIC experienced moderate or worse toxicity. To decrease the potential for error in interpretation of treatment results, histopathological confirmation of diagnosis was undertaken by a panel of reference pathologists; pathology slides were submitted on 97% of entered patients. The on-study clinical diagnosis was affirmed in 199 of 316 patients (63%) with a final review. In 23% of patients, the panel agreed with the diagnosis of soft tissue sarcoma, but not with the type. In 14%, the panel concluded that a diagnosis of mesenchymal malignancy could not be affirmed. Final treatment results were based on the 275 pathologically confirmed, eligible patients. The most common histological subtype entered was leiomyosarcoma (99 patients). The response to Adr-DTIC of this subtype was higher (44%) than that of any other subtype. However, this difference alone was not responsible for the overall superiority of the combination. This confirmed that the combination of DTIC plus Adr adds to the response rate of Adr alone in soft tissue sarcomas. Whether the increased response frequency, without an impact on survival, is worth the significantly greater toxicity remains a subjective judgement that must be made within the context of the individual patient.
This randomized study, conducted by the Eastern Cooperative Oncology Group, compared Adriamycin (doxorubicin) (70 mg/m2) versus vincristine (1.4 mg/m2) and Adriamycin (50 mg/m2); and cyclophosphamide (750 mg/m2) versus vincristine (1.4 mg/m2), actinomycin‐D, (0.4 mg/m2), and cyclophosphamide (750 mg/m2) for treatment of metastatic mesenchymal malignancies. The respective response rate seen in 200 evaluable patients to the treatments were, 27, 19, and 11%. The response rate to Adriamycin was significantly better than the response to vincristine, actinomycin‐D, and cyclophosphamide (P = 0.03, two‐sided). The respective median survivals on the three treatments were 37, 34, and 41 weeks and were not significantly different. Moderate or severe vomiting occurred in 60% of patients receiving vincristine—cyclophosphamide—adriamycin, a greater frequency than in Adriamycin alone (P = .09 two‐sided). Severe or life‐threatening hematologic toxicity (leukocytes <2000, platelets <50,000) occurred in 30% of patients receiving the Adriamycin combination, a markedly increased frequency when compared to the other two regimens (P = 0.07, P = 0.02, two‐sided). This trial establishes that Adriamycin has a better response rate than the combination of vincristine—actinomycin‐D—cyclophosphamide in advanced sarcomas. The combination of vincristine, Adriamycin, and cyclophosphamide increased toxicity and did not add to the therapeutic effect achieved with Adriamycin alone.
Estrogen receptor assays were performed on tumor specimens from 6 male patients with documented breast cancer. Five out of six (83%) males had positive ER assays with values ranging from 23-384 femtomoles per mg cytosol protein. A review of the literature showed that 32 out of 38 patients (84%) reported were positive for estrogen receptor. Four out of five ER positive males responded to orchiectomy. Estrogen receptors are present in a high percentage of males with breast cancer and may predict response to treatment, similar to female breast cancer.
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