[The operated breast cancer. Control and adjuvant chemotherapy].
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Biomedical subjects
Publications and source records attributed to G Martz.
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From 1971 to 1974 89 patients with advanced ovarian cancer (FIGO-stage III-IV), admitted to seven centers of the Swiss Group for Clinical Cancer Research (SAKK), were randomly allocated to three different treatment schedules: cyclophosphamide (CYT) alone or CYT in combination with either medroxyprogesterone acetate (GEST) or 5-fluorouracil (FU). Results in 71 evaluable patients (according to standardized group criterial) were as follows: 1. The overall remission rate was 48% (34 out of 71 patients) with no clear-cut statistical difference between the three treatment schedules but a firm trend towards higher remission rate with CYT + FU (58% as compared to 42% with CYT alone). 2. The scheduled "second-look" operations were performed in only 5 of 34 patients clinically judged to respond to therapy (PR), and does not allow objective surgical monitoring of therapeutic effects intraabdominally. 3. The median remission duration varied from 3 months (CYT alone) to 6 months (CYT + FU or CYT + GEST), again with only marginal statistical differences. 4. With regard to survival from initiation of chemotherapy, no treatment regimen was superior to another. The median survival ranged from 6.6 months (CYT) to 10.3 months (CYT + GEST). Patients responding to chemo-(hormone) therapy (CR + PR + NC) showed a significant prolongation of survival as compared to those with initial disease progression: median survival in "responders" was 11 months and in "non-responders" 2.9 months. A small group of 8-10% of all treated patients has survived in documented tumor remission for 4 years and more. 5. Toxicity was moderate and consisted mainly of mild temporary hematologic depression, tolerable nausea and transient alopecia, with equal distribution in the three treatment regimens. Hemorrhagic cystitis due to CYT was observed only in 3 cases. 6. Progress in remission induction and duration, as well as survival in advanced ovarian cancer, seems to depend on the inclusion of new effective agents (such as adriamycin, hexamethylmelamine and cisplatinum) and, most probably, on significantly more intensive treatment.
The preliminary results of an on-going SAKK study on metastasising mammary cancinoma are reported. At the time of writing 210 cases are already evaluable. This study seeks to investigate the question of the necessary intensity of polychemotherapy and also the problem of whether cytostatic therapy should be begun at the same time as hormonal therapy or just after failure of this measure. At present no definite answer is available. The results point to a new, possibly important aspect of the treatment of metastasising mammary carcinoma.
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A prospective randomized trial by CALGB examined the relative value of four chemotherapy regimens in 537 patients with stage III B and IV Hodgkin's disease. A new combination BOPP, derived by substitution of BCNU for nitrogen mustard in the MOPP regimen, was compared to MOPP and to two 3-drug regimens, derived by removing the procarbazine in BOPP (BOP) or removing the alkylating agent (OPP). The 4-drug programs gave significantly higher frequency of complete remissions (BOPP 67%, MOPP 63%) than the 3-drug regimens (BOP 40%, OPP 42%), and significantly longer duration of remission and survival. BOPP had a therapeutic activity equal to MOPP, and was accompanied by less toxicity. After 6 cycles of induction chemotherapy, responding patients, both CR and PR, were continued on maintenance chemotherapy for 3 years. No significant difference in relapse rate was demonstrated following maintenance treatment with either vinblastine, chlorambucil, or chlorambucil plus monthly vincristine + prednisone doses. Nor could a reinforcement phase late in the maintenance program be shown to influence the relapse rate. The median survival for all patients entered on the 4-drug programs was 5 years, while the median has not yet been reached at 6 years for those patients, who obtained CR.
The preliminary results of a still ongoing phase III study in patients with previously untreated metastatic breast cancer are reported. 210 cases are already evaluable. In this study patients are randomized to hormonotherapy either concurrently with combination chemotherapy or alone, chemotherapy being delayed until the occurrence of tumor progression. In both groups patients are further randomly allocated to 3 chemotherapy programs. So far there appear to be differences between remission rates, but not with regard to survival course.
Many tumors, especially when metastasizing, produce a variety of symptoms. Two frequent sets of complications due to metastasizing cancer (mainly to the bones), i.e. vertebral metastases and chronic pain, are reviewed. In the case of vertebral metastases, the fitting of an orthopedic corset should--and as a rule can--be avoided. Treatment of this complication is by systemic therapy and/or radiotherapy. Symptoms or signs of medullary compression are indications for emergency treatment by the radiotherapist or the neurosurgeon. In the case of chronic pain, regular oral intake of the Brompton mixture is an alternative to injections of analgesics in that it prevents rather than alleviates pain and is only slightly addiction-forming.
The detection of specific hormone receptors in normal and tumor tissue has brought new insight into the mechanisms of action of hormones and anti-hormones. The Swiss Cooperative Cancer Study Group (SAKK) has evaluated the antitumor effect of the new antiestrogenic substance tamoxifen in metastatic breast cancer. 158 postmenopausal patients treated with 20 mg/d tamoxifen by mouth are evaluable at present time. Complete and good partial remissions were achieved in 39 patients (25%) largely with soft tissue but also lung and bone metastases. Tamoxifen was well tolerated and caused few serious complications such as thrombosis/pulmonary embolism and hypercalcemia. These results confirm already published experience with tamoxifen, which may replace the estrogens as the primary endocrine treatment in postmenopausal mammary carcinoma metastasizing to soft tissues, lung and bone.
A short survey of recent progress in the diagnosis and pharmacotherapy of neoplastic diseases is conducted, with special mention of measurement of hormone receptors, needle biopsy, tactics and strategy of drug therapy, and new drugs. The importance of several forms of cooperation is stressed: cooperation between doctor and patient, between hospital physician and town physician, interdisciplinary cooperation, and cooperative clinical studies. Adjuvant chemotherapy and immunotherapy are new methods under study. The problems arising in the wake of progress in medical oncology and the ever increasing use of chemotherapy are loss of individual initiative in physicians working with protocols, and prohibitive costs are diagnostic and therapeutic procedures become more sophisticated.
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Sixteen patients in an acute blast crisis of chronic myeloid leukaemia (CML) were treated with a combination of vincristine, 6-mercaptopurine, hydroxyurea and prednisone. Only two of these patients had complete remission on this treatment, while four had partial remission. This experience, comparable to that reported by others, suggests that aggressive treatment in the terminal phase of CML is justified only as part of a prospective and well-controlled study.
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One hundred and eighteen patients with inoperable carcinoma of the lung were randomly selected for treatment with methotrexate, cyclophosphamide, procarbazine, and vincristine. These drugs were adminsitered simultaneously to one group of patients and sequentially to the second group. As the statistically sicame evident (51% vs. 21%), an additional 85 cases were treated in this manner without randomization. The objective clinical responses were associated with prolonged survival. A higher response rate with the simultaneous treatment was also evident in patients with anaplastic small cell carcinoma (65% vs. 36%) as well as those with epidermoid carcinoma (33% vs. 13%). These differences were not statistically significant. Toxicity remained within acceptable limits, with a 2% drug related mortality, and was similar in both treatment regimens. Initial performance status was definitely related to survival, but not to tumor response. Patients with epidermoid carcinomas showing stabilization of tumor growth under treatment had the longest survival. Maintenance therapy with continued four-drug polychemotherapy was not superior to single agent maintenance with cyclophosphamide.