Current concepts: management of breast cancer.
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Biomedical subjects
Publications and source records attributed to C L Spurr.
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Twenty-eight patients with disseminated malignant melanoma were treated with DTIC (250 mg/m2 iv, Days 1--5) and actinomycin D (0.5 mg/day iv, Days 1--5) at 5-week intervals. Patients were randomly allocated to receive no immunotherapy or immunotherapy consisting of methanol extracted residue of bacillus Calmette-Guérin (0.5 mg intradermally; 100 microgram in five separate sites) every 5 weeks, concomitant with chemotherapy. Of these 28 evaluable patients, 13 received chemoimmunotherapy with one complete response (CR) and 15 received chemotherapy alone with one CR. Both responses occurred in lymph node metastases. No partial responses were seen.
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Twenty-nine patients with small cell carcinoma of the lung and without evidence of brain metastasis were randomized into two treatment groups consisting of 14 patients who received prophylactic cranial irradiation (PCI) and 15 who received none (non-PCI). All patients were treated with irradiation of the primary lesion and concomitant chemotherapy. The response rate and median survival of the two groups were not significantly different: 93% and 7.2 months in the non-PCI; 86% and 9.8 months in the PCI; P larger than or equal to .05. Brain metastasis occurred in 0/14 patients in the PCI and 4/15 in the non-PCI (P less than or equal to .05) and was the cause of major neurologic disability in each. Although PCI did not improve response rate or survival, brain metastasis with its attendant neurologic complications was effectively prevented.
A prospective randomized trial was undertaken to compare the efficacy of a three-drug regimen using cyclophosphamide, methotrexate, and fluorouracil to a five-drug regimen using vincristine sulfate and prednisone in addition to cyclophosphamide, methotrexate, and fluorouracil in advanced breast carcinoma. Seventy-two patients who had received no prior chemotherapy were randomized. Thirty-eight patients received three drugs, and 34 received five-drug therapy. The objective response rates, 34% and 50% respectively, did not differ signficantly (P = .13). As expected, myelosuppression occurred in most patients, and neurotoxicity was much more common in patients receiving vincristine. Three of 12 patients treated with the five-drug regimen after progession of disease while receiving the three-drug regiment showed an objective response to the five-drug regimen.
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Sixteen women with advanced carcinoma of the cervix were treated with adriamycin and methotrexate. Median age on entry into the study was 51 years. Seven subjects were premenopausal, 7 postmenopausal, and 2 were within 2 years of their last menstrual period at the time of diagnosis. Median time of inclusion in the study was 3.3 months. Median survival from initial diagnosis thus far has been 39.0 months. Median survival from the institution of therapy has been 5.8 months. Of 16 evaluable patients the following results were obtained: no complete remissions (0%), 2 partial remissions (12.5%), 1 patient with stable disease (6.2%). When used in dosages which do not precipitate dangerous toxicity this therapy is not effective and in the opinion of the authors should be abandoned.
Mouse leukemia L1210 cells were exposed to continuous wave 2 MHz, 10 W/cm(2) ultrasound for 10 minutes while suspended in nitrogen mustard solution in vitro. Mice subsequently inoculated with these cells had longer survival times than control animals that received cells exposed to the drug but not ultrasound. Without the drug, ultrasound did not alter survival time. Tracer studies revealed increased cellular accumulation of drug under the influence of ultrasound.
Ninety-two patients with advanced bronchogenic carcinoma were prospectively randomized according to performance status, histology, and extent of disease to methyl-CCNU alone; methyl-CCNU and vincristine; or methyl-CCNU, vincristine, and methotrexate. Seventy-three patients were evaluable. Randomization to methyl-CCNU alone was discontinued when only three brief "static" responses were noted in 11 patients and the survival (p less than .01) and time on study (p less than .05) were noted to be significantly less than with the combination. Two of 32 patients treated with methyl-CCNU and vincristine, and two of 30 patients treated with methyl-CCNU, vincristine, and methotrexate had mixed responses with a median of 67.5 days. A static response was seen in eight of 32 and none of 30 patients, respectively. Minimal toxicity occurred in all regimens. Methyl-CCNU alone or in combination with vincristine or vincristine and methotrexate is of limited benefit in patients with lung cancer, although our data suggest (p = 0.15) that the addition of methotrexate increases time on study and survival in patients with extensive disease.
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Three hundred twenty-six patients with acute myelocytic leukemia were randomly and prospectively assigned to four therapeutic regimens: cytosine arabinoside either alone or in combination with daunorubicin, 6-mercaptopurine, or 6-thioguanine. The results in 231 qualified previously untreated patients were analyzed. The combination treatments produced a significantly greater frequency of complete or partial remission than single drug therapy. Treatment with cytosine arabinoside and thioguanine led to 48% age-adjusted complete and partial responses. The median sur survival from diagnosis of all 66 evaluable patients treated with these two drugs was 18 weeks, while the median survival for those who responded to this combination was 15 months.
Thirty-eight patients with metastatic colorecal carcinoma were treated with 5-fluorouracil (5-FU), and 38 patients were treated with the combination of 5-FU, cyclophosphamide, and methotrexate. In terms of percent response, response duration, and survival there was no apparent difference between the two regimens. Combination chemotherapy was found to be effective in 6 of 16 patients refractory to treatment with 5-FU alone, but was associated with more morbidity.
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