Biomedical subjects
Publications and source records attributed to C Louvet.
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.
Ninety-three collections of leucocytes by cytapheresis followed by separation of monocytes by centrifugal elutriation were undertaken in twelve metastatic cancer patients (four melanomas, six colon carcinomas, one ovarian carcinoma, and one lung cancer). The leucaphereses were performed aiming to collect a product, ready for introduction into the elutriation chamber, i.e., with low contamination by erythrocytes and granulocytes. The median collection of leucocytes was 7.3 x 10(9). After elutriation, purified monocytes (mean: 0.91 x 10(9)) were cultured with 3-5% autologous serum for 7 days in the presence of 250 IU/ml of recombinant human gamma-interferon (Rh-IFN gamma) for the last 18 h of culture. The median number of activated macrophages (MAK) available for reinfusion was 2.4 x 10(8) for each culture. The phenotypes and the antitumoral potentiality of MAK cells were documented. Reinfusions performed i.v. or i.p. were well tolerated with no major side effects. No complete tumor response was obtained. One partial response and two stabilizations of the disease were observed in one melanoma and two colon carcinomas.
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.
Lorazepam, dexamethasone and high-dose metoclopramide were given to 54 patients to prevent emesis induced by cisplatin (50-120 mg/m2) on day 1, while prochlorperazine and dexamethasone were administered on days 2 and 3 for control of delayed emesis. Nausea and emesis were recorded from day 1 to day 8. This combination was well tolerated. Prevention on day 1 was complete for 72% of patients and satisfactory (less than or equal to 2 emeses on day 1) in 85%. From days 2 to 8, no emesis, less than or equal to 2 and greater than 2 episodes occurred in 70, 11 and 19%, respectively. Overall control (days 1-8) was complete in 55.5% and satisfactory (less than or equal to 2 emeses on day 1 and/or less than or equal to 2 emeses from days 2 to 8) in 74%. Delayed emesis started on days 2-5. Mean duration was 2.6 days. Delayed nausea or emesis were more frequent when emesis occurred on day 1. Based on data previously reported and on these observations, better ways to prevent delayed events are discussed. Further trials must record systematically delayed side effects.
Eighteen patients with advanced gastric cancer were treated with cisplatin 80 mg/m2 d 1, doxorubicin 30 mg/m2 d 3 and mitomycin-C 12 mg/m2 d 3. One complete and 6 partial responses were observed in 17 evaluable patients (41%, confidence interval 17-65%). Median duration of response was 7 months; median survival was 8 months. One death due to toxicity was observed. This combination of 3 active drugs should not be recommended in cases of gastric cancers.
We studied a series of 42 patients with advanced ovarian cancer who received intraperitoneal chemotherapy post second-look laparotomy. High-dose cisplatin (200 mg/m2) alone or in combination with cytarabine (2 g) achieved 47% response rate. Median overall survival from second-look laparotomy was 44 months with cisplatin (36 cases), 15 months with carboplatin (600 mg/m2, 5 cases) and not reached at 3 yrs with mitoxantrone (25 mg/m2, 8 cases). Median overall and progression-free survival from second-look laparotomy were 44 and 39 months respectively in complete responders (15 cases), 20 months and 9 months where residual tumor less than 2 cm (21 cases), 22 and 12 months where tumor greater than 2 cm (6 cases). There was a significant difference in survival (P = 0.01) and progression-free survival (P = 0.002) between complete responders and patients whose tumor was less than 2 cm. Toxicity was acceptable except for carboplatin with constant grade 4 leukocytes or platelets toxicity. It was not demonstrated that high-dose intraperitoneal chemotherapy given post second-look laparotomy will improve survival in advanced ovarian cancer. Further studies of polychemotherapy or early administration are needed.
Adult T-cell leukaemia is the first blood disease caused by a retrovirus: HTLV-1. The authors report the first French series of 15 patients, of whom 9 came from the classical endemic areas--the Antilles and outer Caribbean Islands--and 6 from Africa where the serological prevalence of HTLV-1 is high but few cases of adult T-cell leukaemia have been reported. Emphasis is laid on the importance of immunodeficiency (refractory strongyloidiasis, Pneumocystis carinii pneumonia, polyclonal B lymphoproliferative syndrome) and of other pathologies associated with the retrovirus (polyarthritis, lymphocytic interstitial pneumonia). The authors also describe the presence of adenopathy in healthy carriers: either adenitis suggestive of retroviral infection, or Castelman's disease adenopathy. These clinical presentations are similar to those described in lymphadenopathy syndromes due to the human immunodeficiency viruses. Aggressive lymphomas require chemotherapy, but sooner or later resistance develops, and the prognosis is very poor. The indications for allogeneic bone marrow transplantation are still to be determined. The diagnosis of adult T-cell leukaemia must be considered in all patients with blood disease coming from the endemic areas.
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Second-look laparotomy (SLL) was performed after chemotherapy in 86 patients with advanced epithelial ovarian cancer. Seventy-one patients received cisplatin-based regimens. Median follow-up was 66 months. Negative SLL was found in 32 patients who had a 5-year survival rate of 48.3% after SLO. Microscopic residual disease was present in seven patients whose 5-year survival rate was 35.7%. Maximum residual tumor of 2 cm or less was found in 13 patients with a 5-year survival rate of 30%. Residual tumor larger than 2 cm after secondary cytoreduction was present in 20 patients; their 3-year survival rate was 19.7%. Fourteen patients with bulky residual disease who did not have cytoreduction were all dead within 17 months. Patients with initial residual tumor at first laparotomy less than 2 cm had a nearly significant advantage in survival rate over patients with residual disease greater than 2 cm and stage IV (P = 0.07). Non-responders to initial chemotherapy had a survival rate similar to that of partial responders. These findings justify discontinuation of conventional systemic chemotherapy for patients showing residual disease after SLL and secondary tumor removal in case of residual tumor at SLL. Therapeutic trials are needed in advanced ovarian cancer testing initial aggressive surgery or early debulking to avoid bulky residual disease, and consolidation therapy in patients who achieved complete pathological response or minimal residual disease.
We report a case of hypercalcemia in a 20-year-old woman with an ovarian seminoma. She had neither evidence of bone metastasis nor hyperparathyroidism. Hypercalcemia was well controlled by corticotherapy and chemotherapy, and remained normal after remission was obtained. Different patterns in paraneoplastic hypercalcemia are detailed, with emphasis on PTH-related proteins and vitamin-D metabolites. Eleven cases of neoplasm with hypercalcemia and elevated calcitriol level are reported in the literature. One of them is a seminoma. These elevated levels could be related either to a PTH-like protein, either to 1 alpha-hydroxylase activity in some tumoral cells. Three other cases of seminoma associated with hypercalcemia without dosage of vitamin-D metabolites are reported. Dosage of calcitriol might be performed in paraneoplastic hypercalcemia of seminoma.