Biomedical subjects
Publications and source records attributed to A de Gramont.
Paclitaxel is a new antimitotic derived from yew-tree, used for the treatment of ovarian and breast cancers. The local toxicity of paclitaxel is still poorly known. We report one of the first observations of accidental subcutaneous extravastion of paclitaxel. Local epidermic necrosis was observed and evolution was good with local treatment only. Treatments of such extravasation are discussed.
AIM OF THE STUDY: To determine the characteristics of 51 cases of isolated local regional breast cancer recurrence. METHODS: Retrospective study from 1980 to 1992, survival calculated according to Kaplan-Meier and log-rank test. RESULTS: Twenty-five patients had had a conservative treatment of her primary tumour, 26 had been treated by modified radical mastectomy. Local regional recurrence rate was 9%: 44% of recurrences after lumpectomy and 43% of recurrences after mastectomy occurred within 2 years after the initial treatment. Site of local regional recurrence was chest wall only (16 cases), breast only (15 cases) or axillary or supraclavicular node with or without chest wall or breast involvement (20 cases). The actuarial 5-year survival rate after recurrence is 54%. It depends on the time to recurrence (40% if time to recurrence was less than 2 years, 68% if more than 2 years, p < 0.10), on initial node involvement (36% for N+, 71% for N-, p < 0.15) and on the site of recurrence (chest wall: 43%; breast: 48%; regional node: 12%, p < 0.10). CONCLUSION: Like in the literature, severe recurrences are early recurrences, lymph node recurrences and recurrences following a primary tumour with involved axillary nodes.
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A 58 year-old woman was hospitalized for an hemorrhagic stroke, associated with a consumption's coagulopathy, related to a stage Ic ovarian carcinoma. After surgery and chemotherapy, hemostasic disorders disappeared. The same disorders occurred at tumoral relapse. Relationships between thrombotic or haemorrhagic manifestations and neoplasms are discussed, with emphasis on singularity of such phenomenon in ovarian carcinoma.
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Signal transduction through ligation of the CD23 (Fc epsilon RII) molecule was analysed in human B cells and monocytes. Monoclonal antibodies directed against the IgE binding site of CD23 were found to trigger phosphoinositide hydrolysis and calcium mobilization in B cells, but not in monocytes. These early events were also obtained with an IgE+anti-IgE complex, which supposedly mimicks the physiological situation of a multivalent antigen inducing the cross-linking of cell-bound IgE. Redistribution of CD23 was also found to evoke cAMP accumulation both in B lymphocytes and monocytes. Moreover, we present evidence indicating a possible cross-talk between the IL-4- and CD23-induced second messengers. We suggest that the alternative transduction pathways elicited by ligation of CD23 are linked to the CD23 isoform(s) expressed by these cells and may result from their association with different sets of molecules.
60 patients with metastatic breast cancer were entered in a phase II study using folinic acid, 5-fluorouracil bolus and infusion and mitoxantrone with or without cyclophosphamide. 47 had measurable visceral metastases and 13 had exclusively bone metastases. 36 had received previous adjuvant or metastatic treatment (33/36 with anthracycline-based regimens). Overall response rate in visceral metastatic patients was 57.1% [95% confidence interval (CI) 35.4-78.8%]; 45.5% and 70% in previously and non-previously treated patients, respectively; duration of response was 9 and 13 months, respectively. 10 out 13 patients with exclusive bone metastases improved for a median time of 18 months. Median survival was 22 months for the 60 patients; 18 and 31 months for previously and non-previously treated patients, respectively. Cyclophosphamide was scheduled only in the absence of nadir grade 4 neutropenia. However, this toxicity occurred in the first 7 patients. For this reason, we chose to avoid cyclophosphamide in patients over 60 years, or with a performance status of 1-2, or who had received previous chemotherapy. Overall, cyclophosphamide was stopped due to nadir grade 4 neutropenia in 17/24 patients for whom this drug was planned. When mitoxantrone, 5-fluorouracil and folinic acid were used at the doses scheduled, the addition of cyclophosphamide appeared feasible in only about 25% of the patients. Furthermore, survival was identical for patients receiving or not receiving cyclophosphamide. Therefore, cyclophosphamide does not contribute substantially to this regimen. This study confirms the value of folinic acid, 5-fluorouracil and mitoxantrone in metastatic breast cancer.
We studied the levamisole toxic effects in adjuvant therapy for colorectal cancer. The therapy toxic effects on 127 patients were statistically more important in the levamisole-treated group compared to patients treated with folinic acid and 5-fluorouracil alone. Randomized studies in progress will demonstrate the real therapeutic value of levamisole.
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40 patients with advanced ovarian cancer were treated with immediate debulking followed by sequential cisplatin and doxorubicin every 4 weeks, followed by second-look laparotomy (SLL). Six courses were given when residual disease (RD) was under 2 cm. When RD was over 2 cm, three courses were followed by early debulking and six more courses before SLL. Immediate debulking was optimal in 15 patients (38%) and early debulking in an additional 15 (38%). Pathological complete responses (34 evaluable cases) were observed in 14 cases (41%), partial response in 13 (38%), stable disease in 3 (9%) and progression in 5 (15%). Toxicity was mainly haematological. 11 patients with negative SLL and 15 with RD under 2 cm received intraperitoneal cisplatin 200 mg/m2 alone or with cytarabine. Median survival was 45 months: 58 months for RD under 2 cm at initial laparotomy and 31 months for RD over 2 cm. Median survival was 46 months when early debulking was successful. 5 year disease-free survival was only 16%. However, this multimodal treatment offers prolonged survival, especially in patients optimally debulked either at initial laparotomy or at early debulking surgery.
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Twenty patients with documented progression after two or three cisplatin-based regimens for advanced epithelial ovarian carcinoma were treated with high-dose folinic acid (200 mg/m2), 5-fluorouracil bolus (400 mg/m2) and continuous infusion (600 mg/m2) for two consecutive days every two weeks. One clinically complete and two partial responses were observed in 16 evaluable patients, with 5 remaining stable. Median survival was 9 months. Toxicity was mild. This combination achieved a 19% (95% confidence interval 4%-46%) response rate in heavily pretreated cisplatin-resistant patients.
We studied survival in 36 patients with Stage III/IV ovarian cancer who received intraperitoneal high-dose cisplatin (200 mg/m2) alone or in combination with cytarabine (2 g), after intravenous (i.v.) cisplatin-based chemotherapy followed by second-look laparotomy. Complete responders were scheduled for three courses of IP chemotherapy, and others for six. Eight patients (22%) did not complete treatment (6 catheter failures and 2 renal failures). Peritoneal cytology remained positive in 6 patients (17%). Median overall and progression-free survival after second-look laparotomy were 44 and 37 months, respectively, for 13 complete responders to i.v. chemotherapy; 24 months and 11 months for patients with residual tumors less than 2 cm (17 cases); 15 and 12 months with tumors greater than 2 cm (6 cases). There was a significant difference in overall (p = 0.05) and progression-free (p = 0.001) survival between complete responders to i.v. chemotherapy and patients whose tumor was less than 2 cm. We find no evidence that high-dose cisplatin-based intraperitoneal chemotherapy given after second-look laparotomy will enhance survival in advanced ovarian cancer with zero or minimal residual disease.
Two patients treated by radiotherapy, one 13 years previously for Hodgkin's thymoma and the other 10 years previously for breast cancer, presented with a radiation-induced sternal tumour. The first case had undergone manubriectomy for fibrosarcoma complicated by dehiscence of the skin wound one year prior to referral to our unit: she presented with a haemorrhagic ulcerated recurrence. The lesions were widely excised (skin defect: 13 x 13 cm). The second patient underwent "en bloc" cutaneo-osteomyopericardectomy with omentoplasty onto the pericardium and sternal prosthesis (skin defect: 12 x 7 cm). These tumours are rare, but the radiation-induced skin damage requires wide excision. In both cases, the skin defect was easily repaired by means of a latissimus dorsi myocutaneous flap.
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We report an additional cytogenetic study of a metastatic Merkel cell carcinoma. Even though the cells analyzed were from a metastatic lesion, chromosomal abnormalities were not complex. Similarities between cytogenetic findings described in small-cell lung carcinoma and the present case are observed. However, further studies are needed to define the relationship between these two neuroendocrine small-cell malignancies.
Plasma cell leukemia (PCL) is a very rare disease. We report two cases of PCL with complex chromosomal abnormalities: long arm trisomy and short arm partial monosomy of chromosome 1, a marker derived from chromosome 8, and monosomy 13 were found in both cases; other additional chromosome abnormalities were also present in each case. Bastard et al. reports two similar cases in this issue. Cytogenetic studies in PCL have seldom been reported in the literature: chromosomal abnormalities are most often complex: chromosomes 1, 8, 11, 13, and 14 are those most frequently involved. Such cytogenetic findings are observed in advanced multiple myeloma. Cytogenetic, clinical, and immunological findings observed in PCL and the advanced stage of multiple myeloma are arguments for the single origin of pathogenesis.
Twenty-five patients with advanced measurable gastric cancer were treated with high-dose folinic acid (200 mg/m2), 5-fluorouracil bolus (400 mg/m2) and continuous infusion (600 mg/m2) for two consecutive days every two weeks. Fourteen patients over 65 yr old and/or with a poor general status received first-line treatment, and eleven younger patients second-line. The response rate was 43.5% in 23 evaluable patients. There were 2 complete responses (8.7%) and 8 partial responses (34.8%). Median survival was 6 months in first-line and 8 months, calculated from start of folinic acid-5FU, in second-line. Toxicity was mild without WHO Grade greater than 2 events. This combination is effective for advanced gastric cancer in poor-prognosis patients and requires further studies.