Biomedical subjects
Publications and source records attributed to J F Morere.
In 23 patients with peritoneal, pleural oder pericardial metastases the efficacy of intracavitary tumor therapy was investigated. 5-FU was administered intracavitary in all patients combined with systemic chemotherapy. 8 partial responses (34%) were achieved.
The action of piroxicam, an inhibitor of prostaglandin synthesis, was evaluated in 31 cases of measurable pulmonary metastases of several primary cancers. In each case, the spontaneous doubling time was measured prior to and after a minimum of 3 months of treatment with piroxicam as a single drug, 20 mg daily po. The doubling time of metastatic lung nodules was significantly increased in 18/31 cases (58%) of which 10 cases had their spontaneous doubling time multiplied by two. Minor regressions were observed in 5/31 cases (16%) and one case of metastatic fibrosarcoma had a complete radiologic response. No effect was observed in 8/31 cases (26%). Prostaglandin synthesis inhibitors may be useful for treating metastatic cancer. Possible mechanisms of action are discussed.
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Sweat gland carcinoma is a rare malignant tumor considered to be radio- and chemo-resistant. A case affecting a labium majorum recurred after surgical resection and was accompanied by bone and visceral metastases. After four cycles of combination chemotherapy consisting of doxorubicin, mitomycin C, vincristine and cisplatin, complete remission lasting 16 months and prolonged survival (50 months) were obtained. A review of the literature also is presented.
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Twenty-five consecutive cases of inflammatory breast carcinoma were treated with high-dose cyclophosphamide and 5-fluorouracil in 5-day courses every 3 weeks for 2 years, with total mastectomy performed after the third course. The toxicity was high but acceptable in 24 of the patients, provided the doses were decreased. Tumor was found at surgery in all 24 patients, and the lymph nodes were involved in 19 of 24 cases. The median follow-up was 35 months (range, 16-76 months). Thirteen relapses were observed, three of which were exclusively locoregional. The median disease-free survival was 46 months. The expected median survival is greater than 6 years. Six patients were treated with radiotherapy for regional recurrences. The good results obtained with this severe form of the disease confirm: that chemotherapy is highly effective in primary tumors and that initial radiotherapy is not necessary in the management of this disease.
Six hundred and eighty seven cases of cancers of various sites, essentially of squamous structure are presented. Their treatment consisted of a combination of cisplatinum, given 5 days in a row every 3 weeks and of continuously infused bleomycin, also 5 days every 3 weeks. Objective (greater than 50 p. 100) regressions were seen in 70 p. 100 of cases, a significantly greater proportion than obtained by other chemotherapies or by cisplatinum and bleomycin given for one day. This difference is attributed to the fact that bleomycin, a potent inhibitor of type II DNA polymerase, inhibits DNA repair. The authors evaluate the extent of DNA repair to be about 80 p. 100 of all the lesions created by platinum salts and consider DNA repair to be a major limitation of cytostatic therapy, often neglected in the design of chemotherapy protocols.
Palliative chemotherapy in cases of epidermoid bronchogenic carcinoma, initially judged to be inoperable, made it possible to perform operative resection in 50 cases. An association of cis-platinum and bleomycin was used, this combination having previously been considered synergistic. In certain cases the tumour seemed to have disappeared on macroscopic examination of the resected specimen, and in some instances no tumoral cells could be found on histological examination. This series brought out several positive features: chemotherapy made it possible to operate on patients previously judged to be inoperable; it ensured maximum local efficiency of drugs because of the absence of abnormal vascularity; and it made it possible to anticipate the cure of occult metastases. However, three negative aspects were also present: modification of postoperative TNM classification making it difficult to establish a prognosis; difficulty in determining therapeutic strategy for pNo; and inadequate long-term follow-up. On the whole the positive points appeared to outweigh the negative aspects, but a randomized study is necessary to confirm this.
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Between November 1979 and October 1981, 110 consecutive patients with previously untreated, biopsy-proven squamous cell carcinoma of the head and neck, were treated by chemotherapy prior to scheduled surgery and/or radiotherapy. Two regimens of chemotherapy were used. The first 57 patients received cis-platinum, 20 mg/m2/day for 5 consecutive days and bleomycin 5 mg/m2/day as a continuous infusion over the same 5 days every 3 weeks (Regimen A). The next 53 patients received the same schedule and dose of cis-platinum, bleomycin 2.5 mg/m2 every 12 hours for the same 5 consecutive days and mitomycin C6 mg/m2 on day 1 of each cycle every 3 weeks (Regimen B). The number of courses administered prior to surgery and/or radiotherapy ranged from 1-4 depending on the otorhinolaryngologist's assessment of the optimal time for locoregional treatment. The overall response rate in regimen A was 78% (45/57) compared to 90% for regimen B (48/53). Complete responses were seen in 10/57 (18%) and 13/53 (25%) patients in regimens A and B, respectively. Eight of 57 patients in regimen A and 6/53 in regimen B refused further treatment and follow-up, and 7/53 patients in regimen B chose to pursue chemotherapy (in which methotrexate replaced bleomycin) rather than undergo surgery and/or radiotherapy. Five of these seven patients are surviving disease-free from 7-12 months. In regimen A, 31/57 patients are surviving with a median survival exceeding 15 months. In regimen B, 46/53 patients are surviving up to 14 months. Nausea and vomiting induced by cis-platinum were the major side effects, seen to a variable degree in all patients. No cis-platinum-induced renal toxicity was observed with the 5-day regimen and none of the patients had symptomatic bleomycin-induced pneumonitis. One patient had a bleomycin-induced skin rash which did not require discontinuation of therapy.
BACKGROUND: The good efficacy-toxicity ratio of both docetaxel and gemcitabine in non-small cell lung cancer (NSCLC) stimulates the investigation of the combination of these drugs as a first line chemotherapy. This two-step study firstly aimed at determining the maximum tolerated and recommended doses of docetaxel given every 3 weeks in combination with a fixed dose of gemcitabine; the phase I study paid particular attention to pharmacokinetics. Afterwards, the safety and efficacy of the recommended dose was carefully assessed in the phase II-step. METHODS: The following range of docetaxel dosages were tested in the phase I study; 60, 75, 85, and 100 mg m(-2) given on day 8 in combination with gemcitabine 1000 mg m(-2) delivered on days 1 and 8 of a 3-week cycle. Haematopoietic growth factors were not allowed. The treatment was delivered on an outpatient basis. Main eligibility criteria consisted of stage III b or IV histologically proven NSCLC, Eastern Co-operative Oncology Group (ECOG) performance status PS < or =2, age < or =70 years, measurable disease, adequate blood counts, chemistry, and no symptomatic brain metastasis. RESULTS: Four centres enrolled 49 patients (eight having been pre-treated); 16 in phase I and 33 in phase II. The maximal tolerated dose was almost reached at the last dose level (i.e. docetaxel, 100 mg m(-2)). Consequently, we considered the 85 mg m(-2) level as the recommended dose. There was a positive relationship of the docetaxel dose to the area under the curve of this drug. Toxicity was assessable in all patients. Among the 200 cycles delivered, 192 were assessable for this feature. Main toxicity was grade 3-4 neutropenia affecting 23 patients (47% of the population; 23% of the cycles). Six febrile episodes were recorded leading to two treatment-related deaths. Another patient died from congestive cardiac failure. In addition, six patients experienced interstitial pneumonitis, (one half considered as severe), two of them having received the recommended dose. All patients recovered from this toxicity after corticosteroids. Fourteen patients out of the whole population (29%; 95% CI [17-43], including ten patients receiving the recommended dose), achieved an objective response. Median follow-up was 14 months (range, 0.3-29.4). Median survival was 11.2 months (95% CI [8.3-13.2]), and the 1-year survival rate was 45%. CONCLUSION: Gemcitabine, 1000 mg m(-2) days 1 and 8 in combination with docetaxel, 85 mg m(-2), day 8, given every 3 weeks could be considered as an active regimen with manageable toxicities in locally advanced or metastatic NSCLC. This study deserves further comparisons with classical platinum-based regimens.
The effects of two dextran derivatives (CMDBS-6 and CMDBS-12) on the growth rates of three human mammary epithelial cell lines (HBL100,HH9 and MCF7) were studied. CMDBS-6 markedly inhibited the growth of all lines, while CMDBS-12 and native dextran T40 had no effect on the growth of all lines. This inhibition was dose-dependent, reversible and inversely related to the concentration of fetal calf serum. The inhibitory effect of CMDBS-6 is cytostatic but not cytotoxic. Moreover, CMDBS-6 appears to have a stronger effect on HBL100 cells which are non-tumorigenic in nude mice. In contrast, the growth of HH9 cells, which are highly tumorigenic in nude mice, is less inhibited by CMDBS-6. Whereas CMDBS-6 inhibited the HBL100 cell anchorage, that of HH9 cells was not affected. By analysing the cell distribution in the various phases of the cell cycle, we have observed that CMDBS-6 arrested HBL100 and MCF7 cell mainly in the G0/GI phase. In contrast, HH9 cells were accumulated in the G2/M phase. When treated with CMDBS-6, human mammary cells slightly increased their granularities. These results demonstrate an antiproliferative activity of CMDBS-6 which could not be explained by an inactivation of mitogens provided by the serum but suggest that this compound could exert its cytostatic effects via a cell-specific mechanism.