Randomized adjuvant study comparing two schemes of 5-fluorouracil and leucovorin in stage B2 and C colon adenocarcinoma: study design and preliminary safety results. Groupe d'Etude et de Recherche Clinique en Oncologie Radiotherapies.

The aim of this randomized open-label study was to compare a bimonthly with a monthly regimen of 5-fluorouracil (5-FU) and leucovorin for the adjuvant treatment of colon and high-rectum adenocarcinoma. The bimonthly regimen was administered for 2 consecutive days every 14 days as d,L-leucovorin 200 mg/m2 or L-leucovorin 100 mg/m2 as a 2-hour infusion followed by 5-FU bolus of 400 mg/m2 and a 600 mg/m2 5-FU 22-hour continuous infusion (LVSFU2). In the monthly regimen, d,L-leucovorin 200 mg/m2 or L-leucovorin 100 mg/m2 15-minute infusion followed by a 400 mg/m2 15 minute 5-FU bolus was administered for 5 consecutive days every 28 days (FUFOL). Nine hundred five patients with recently resected stage B2 or C colon or high-rectum adenocarcinoma (inferior pole of the tumor subperitoneal) were recruited into the study. Patients were randomized in a 2 x 2 factorial design to receive either LV5FU2 or FUFOL for 24 or 36 weeks. Characteristics of the patients in the two different treatment groups were similar at baseline. Compliance was good. Mean 5-FU dose intensities were 930 mg/ m2/wk and 463 mg/m2/wk for LVSFU2 and FUFOL, respectively. The incidence of maximal grade III-IV toxicities for LVSFU2 and FUFOL was neutropenia 6% and 16% (P < .001), diarrhea 4% and 10% (P < .001), and mucositis 2% and 7% (P < .001), respectively. Maximum grade III-IV toxicities in the LV5FU2 treatment group were significantly lower than in the FUFOL group (10% v 26%; P < .001). Although patients in the LV5FU2 group received twice the dose of 5-FU compared with those in the FUFOL group, LV5FU2 was shown to be less toxic. Efficacy data will be available in 2001.

Testicular neoplasm presenting as a major pulmonary embolism.

OBJECTIVE: To report an unusual and life-threatening presentation of a nonseminomatous germ cell tumor of the testis. METHODS: A 35-year-old male presented with pulmonary embolism secondary to a neoplastic thrombus from a nonseminomatous germ cell tumor. Prompt management involved surgical thrombectomy with cardiopulmonary bypass and deep hypothermic circulatory arrest, followed by orchiectomy and adjuvant chemotherapy. RESULTS: Three years later, the patient remains disease free according to physical examination, radiographic workup and serum markers. CONCLUSION: The excellent long-term outcome of this patient supports an aggressive multidisciplinary management of nonseminomatous germ cell tumors in young adults.

[Cerebral hemorrhage disclosing metastatic choriocarcinoma]. / Hémorragie cérébrale révélatrice d'un chorio-carcinome métastasé.

We report the case of a 28-year-old woman who presented with multiple episodes of cerebral bleeding secondary to a choriocarcinoma with brain, lung and abdominal metastases, which had been partially treated 1 year before. The diagnosis was confirmed by a-high serum beta HCG level. This case emphasizes the importance of suspecting an underlying choriocarcinoma and obtaining a serum beta HCG level in young women presenting with a cerebral haemorrhage.

High failure rate of carboplatin-etoposide combination in good risk non-seminomatous germ cell tumours.

24 patients with good risk non-seminomatous germ cell tumours (GR-NSGCT) were enrolled in a phase II trial combining carboplatin (C) and etoposide (E). Carboplatin was given at a fixed dose of 450 mg/m2 at d2, and E 120 mg/m2, dl-3, every 4 weeks x 4 cycles (cy). Myelosuppression was the major toxicity with neutropenia grade 4 in 18 cy (19%) and grade 3 in 26 cy (27%). Thrombocytopenia grade 3 and 4 occurred in 7 and 1 cy, respectively. Responses included: 20 complete responses (CR) (83%) with 16 clinical CR and 4 pathological CR; 3 additional patients had complete surgical removal of residual disease (SRRD) with viable tumour (surgical CR); 1 patient progressed during C+E therapy. 5 of the 16 clinical CR relapsed, and all the 3 surgical CR progressed despite post-operative salvage chemotherapy. Adverse events occurred in 9 patients (37.5%; 95% C.I., 19-59%). After a median follow-up of 24 m (range 14 to 38) 4 patients had died [3 progressive disease (PD), 1 suicide while in CR], 3 were alive with PD, and 17 had no evidence of disease. No significant correlation between area under the curve values of carboplatin, overall treatment failure and the platelet nadirs was observed. We conclude that the efficacy of the C+E regimen as given in our protocol is inferior to the standard cisplatin-containing regimens. The low dose-density (D/I) of carboplatin could be responsible for the high failure rate.

Phase I clinical trial and pharmacokinetic evaluation of doxorubicin carried by polyisohexylcyanoacrylate nanoparticles.

Doxorubicin (DXR) incorporated into biodegradable acrylate nanoparticles such as polyisohexylcyanoacrylate (PIHCA) has been shown to increase DXR cytotoxicity and reduce cardiotoxicity by modifying tissue distribution in preclinical studies. We have conducted a phase I clinical trial of DXR-PIHCA in 21 patients with refractory solid tumors (10 male, 11 female, median age: 53 years, median PS: 1, prior free-DXR therapy: 7 patients). A total of 32 courses at 28 day intervals were administered at 6 dose levels (15, 30, 45, 60, 75 and 90 mg/m2). The drug was given as a 10 minute IV infusion on day 1 to the first 5 patients: 2 of them presented a grade 2 allergic reaction (W.H.O. criteria) during infusion, which was rapidly reversible once drug administration was discontinued. Subsequently, in the other 16 patients, the administration was modified to a 60 minute i.v. perfusion diluted in 250 cc of Dextrose 5%: only 1 patient presented the same allergic reaction. Grade 2 fever and vomiting occurred in 9 patients and 7 patients respectively during the first 24 h after treatment. There was no cardiac toxicity among the 18 evaluable patients. Grade 3 or 4 hematologic toxicity occurred at the 75 and 90 mg/m2 dose level. The dose limiting toxicity was neutropenia. The maximum tolerated dose was 90 mg/m2 and the recommended phase II dose was 75 mg/m2. A pharmacokinetic evaluation of DXR-PIHCA was conducted in 3 patients each at a different dose level (60, 60 and 75 mg/m2) and was compared with free DXR given to the same patients in the same conditions.

Ovarian dysgerminoma metastatic to the breast.

A 16-year-old girl underwent a right salpingo-oophorectomy for a pure dysgerminoma limited to the right ovary. One month later, she developed a right pelvic mass along with abdominal lymphadenopathies, peritoneal carcinomatosis, left breast mass, and left axillary node. Cytology of the breast mass was suggestive of a pure dysgerminoma. Breast metastases of epithelial ovarian carcinoma are uncommon. In the literature, this is the first case of a breast metastasis of an ovarian dysgerminoma.

Non-nephrotoxic empiric antimicrobial therapy in febrile neutropenic cancer patients.

We evaluated the efficacy of piperacillin-pefloxacin as a non-nephrotoxic antibiotic combination in febrile neutropenic cancer patients treated with nephrotoxic chemotherapy. 40 patients: 34 with solid tumours and 6 with non-Hodgkin lymphoma, were treated during 55 episodes with: piperacillin 4 g intravenously every 8 h and pefloxacin 400 mg intravenously every 12 h. If the patient remained febrile after 72 h, 1 g vancomycin intravenously was added every 12 h. The mean duration of neutropenia was 7 days (range 3-13). Infection was microbiologically documented in 13 episodes (8 gram-positive cocci and 7 gram-negative bacilli). Temperature became normal in 38 patients with piperacillin-pefloxacin and 12 further episodes were resolved by the addition of vancomycin. 2 patients had an early change of antibiotics because of clinical deterioration, there were 2 protocol violations and 1 patient's temperature became normal after the addition of amphotericin. Neither septic death nor toxicity were observed. We conclude that this empirical treatment is active and safe and warrants further comparative trials.

[Value of the combination of piperacillin and pefloxacin possibly followed by vancomycin in the treatment of febrile neutropenia in nephrotoxic chemotherapy]. / Intérêt de l'association pipéracilline-péfloxacine suivie éventuellement par la vancomycine dans le traitement des neutropénies fébriles au cours des chimiothérapies néphrotoxiques.

We evaluated the efficacy and safety of piperacillin-pefloxacin potentially associated to vancomycin as a non nephrotoxic antimicrobial therapy in febrile neutropenic cancer patients, treated with nephrotoxic chemotherapy. Fifty-seven patients: 49 with solid tumors and 8 non-Hodgkin lymphomas, were treated during 85 episodes with: piperacillin 4 g IV every 8 h pefloxacin 400 mg IV every 12 h. If the patient remained febrile after 72 h, 1 g of vancomycin IV was added every 12 h. The mean duration of neutropenia was 7 days (3-14 days). In 44 episodes, the granulocyte nadir was < 100/mm3. Infection was microbiologically documented in 17 episodes (20%) with ten Gram-positive cocci and 11 Gram-negative bacilli. There were 64 apyrexia with piperacillin-pefloxacin (75%) and further 14 were resolved by the addition of vancomycin (total success = 92%); three early changes because of clinical deterioration (two episodes) or germ resistance (one episode); three protocol violations, and one apyrexia by addition of amphotericin. Neither septic death nor toxicity were observed. We conclude that this empirical treatment is active and safe and avoids nephrotoxicity in cancer patients heavily treated with nephrotoxic chemotherapy.

[Choroid metastasis in a case of urothelial carcinoma metastatic from the bladder]. / Métastase choroïdienne dans un cas de carcinome urothélial métastatique de la vessie.

A 40 year old male, presented with a left choroidal metastases, 2 month after a radical cystectomy for an infiltrating transitional cell carcinoma of the bladder. This localisation was associated with disseminated metastasis which failed to respond to chemotherapy. The patient died within one month. The review of the literature confirms the poor prognosis of choroidal metastases in patients with transitional cell carcinoma of the bladder.

M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for advanced carcinoma of the bladder. The French Federation of Cancer Centers experience.

70 patients with advanced transitional cell carcinoma of the bladder received methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC). Complete responses (CR) were obtained in 13 of the 67 (19%) evaluable patients and partial responses (PR) in 25 patients for an objective response rate of 57% (95% CI 45-69%). Of the 54 patients who have had a minimum follow-up of 2 years, 8 patients (15%) are disease-free or have stable residual disease. Median survival of the 70 patients was 13 months. Toxicity was acceptable with no drug-related deaths. Because of myelosuppression, only 15 patients (21%) received treatment without delays in drug administration or modifications from the planned schedule. Our results confirm that this regimen is effective, with some patients being long-term survivors.

[8;21 translocation and leukemia]. / Translocation 8;21 et leucémisation.

The authors report their observations on acute myeloid leukemias associated with the 8;21 translocation. Two cases have less than the required percentage of blasts for the cytological diagnosis of acute myeloid leukemia. In one case, the 8;21 translocation is superimposed on a constitutional trisomy 21. Conclusions from the 4th International Workshop on chromosomes in leukemia are highlighted, as well as certain new data relative to the biology of acute myeloid leukemias.

Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients.

Three-hundred thirty-two cases of pleural diffuse malignant mesothelioma (DMM) seen at large centers in Ontario and Quebec from 1965 to 1984 were reviewed retrospectively. Previous asbestos exposure was found in 44% of patients. Diagnosis was most often made by exploratory thoracotomy; pleural biopsy or cytology were rarely contributory. The delay in diagnosis was often long (median time, 3.5 months) and thrombocytosis (platelets greater than or equal to 400,000/microL) was common (41% of cases). The median survival (MS) was only 9 months. Eleven clinical variables were analyzed for prognostic significance. The three most important prognostic factors using a univariate analysis were stage, weight loss, and histologic type. For 118 patients with complete data, multivariate analysis showed that the stage of disease, high platelet count, and asbestos exposure were the most important prognostic factors. There was no cure of DMM, and we did not find any drastic differences in survival among groups of patients subjected to the different therapeutic measures. Radical surgery and radiotherapy were ineffective and we confirmed the low response rate to chemotherapeutic agents. This large retrospective trial can serve as a baseline for future studies in this field. In particular, it provides the basis for appropriate stratification variables to be used in future therapeutic trials.