Clinical value of serum glycoprotein galactosyltransferase levels in different histological types of ovarian carcinoma.

Serum glycoprotein galactosyltransferase levels were determined in 28 healthy women and 113 patients with ovarian carcinoma with various histological types, at different clinical stages. Ovomucoid, which possesses terminal N-acetylglucosaminyl residues, was used as glycoprotein acceptor. Clinical correlations between galactosyltransferase levels and tumor burden were examined, as well as the variations due to histology. Follow-up studies could be done for 60 patients, and correlations with clinical evolution, established. Galactosyltransferase might be a promising marker for the diagnosis and follow-up of ovarian carcinomas.

Quality of life in long-term survivors of testicular cancer: a population-based case-control study.

PURPOSE: To evaluate quality of life and social problems in long-term survivors of testicular cancer. PATIENTS AND METHODS: In 1998, 71 testicular cancer survivors (cases) identified from the Calvados General Tumor Registry were enrolled onto a case-control study. One hundred nineteen healthy control subjects (controls), matched by age and location of residence, were selected at random from electoral rolls. Three self-administered questionnaires were used: two health-related quality-of-life questionnaires (Short Form-36 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 core questionnaires) and one life situation questionnaire. Specific questions concerning sexuality were also added. RESULTS: With a mean follow-up of 11 years, health-related quality-of-life scores did not differ significantly between cases and controls, nor did general symptom scores. Psychosocial problems were reported equally by cases and controls. Cases reported more modification of sexual life (P =.04) with decreased sexual enjoyment (P <.01), decreased desire (P =.02), and infertility (P <.01). Cases did not report more divorce than controls; they reported fewer changes in relationships with friends (P =.03). Although a similar proportion of cases and controls were at work, cases expressed less ambitious professional plans (P =.002). Cases had greater difficulty in borrowing from banks (P <.001). CONCLUSION: French long-term survivors of testicular cancer do not express more impairment of health-related quality of life or familial or professional life in comparison with healthy men. They did have more sexual life problems and found difficulty in borrowing from banks. This information should be used by practitioners to help their patients cope with their disease and return to normal life.

Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer.

PURPOSE: Topotecan and paclitaxel were evaluated in a randomized, multicenter study of patients with advanced epithelial ovarian carcinoma who had progressed during or after one platinum-based regimen. PATIENTS AND METHODS: Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 112) or paclitaxel (175 mg/m2) infused over 3 hours every 21 days (n = 114). Patients had bidimensionally measurable disease and were assessed for efficacy and toxicity. RESULTS: Response rate was 23 of 112 (20.5%) in topotecan-treated patients and 15 of 114 (13.2%) in paclitaxel-treated patients (P = .138). Disease stabilization for at least 8 weeks was noted in 30% of patients with topotecan and 33% of patients with paclitaxel. Median durations of response to topotecan and paclitaxel were 32 and 20 weeks, respectively (P = .222) and median times to progression were 23 and 14 weeks, respectively (P = .002). Median survival was 61 weeks for topotecan and 43 weeks for paclitaxel (P = .515). Response rates for topotecan and paclitaxel were 13.3% versus 6.7% (P = .303) in resistant patients (not responded to prior platinum-based therapy or progressed within 6 months of an initial response) and 28.8% versus 20.0% (P = .213) in sensitive patients (progressed > 6 months after response). Neutropenia was significantly more frequent on the topotecan arm 79% versus paclitaxel arm 23% (P < .01). It was short-lasting and noncumulative in both arms. Nonhematologic toxicities were generally mild (grades 1 to 2) for both agents. CONCLUSION: Topotecan has efficacy at least equivalent to paclitaxel manifested by the higher response rate and significantly longer time to progression.

Clinical evidence for topotecan-paclitaxel non--cross-resistance in ovarian cancer.

PURPOSE: A large, randomized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity. In this study, a number of patients crossed over to the alternative drug as third-line therapy, ie, from paclitaxel to topotecan and vice versa. We therefore were able to assess the degree of non-cross-resistance between these two compounds. PATIENTS AND METHODS: Patients who had progressed after one platinum-based regimen were randomized to either topotecan (1.5 mg/m(2)/d) x 5 every 21 days (n = 112) or paclitaxel (175 mg/m(2) over 3 hours) every 21 days (n = 114). A total of 110 patients received cross-over therapy with the alternative drug (61 topotecan, 49 paclitaxel) as third-line therapy. RESULTS: Response rates to third-line cross-over therapy were 13.1% (8 of 61 topotecan) and 10.2% (5 of 49 paclitaxel; P =.638). Seven patients who responded to third-line topotecan and four patients who responded to paclitaxel had failed to respond to their second-line treatment. Median time to progression (from the start of third-line therapy) was 9 weeks in both groups, and median survival was 40 and 48 weeks for patients who were receiving topotecan or paclitaxel, respectively. The principal toxicity was myelosuppression; grade 4 neutropenia was more frequent with topotecan (81.4% of patients) than with paclitaxel (22.9% of patients). CONCLUSION: Topotecan and paclitaxel have similar activity as second-line therapies with regard to response rates and progression-free and overall survival. We demonstrated that the two drugs have a degree of non-cross-resistance. Thus, there is a good rationale for incorporating these drugs into future first-line regimens.

Carboplatin plus paclitaxel in the first-line treatment of advanced ovarian cancer: preliminary results of a phase I study.

This phase I trial was designed to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 3-hour infusion in combination with carboplatin (400 mg/m2) as first-line chemotherapy for stage IIIC/IV ovarian adenocarcinoma. After premedication, paclitaxel was infused over 3 hours, followed by carboplatin infused over 30 minutes on day 1 of a 28-day cycle (group 1, with 28 patients accrued and 150 evaluable cycles) or on day 1 of a 21-day cycle (group 2, with 16 patients accrued and 55 evaluable cycles). Dose-limiting toxicities assessed after the first course included grade 4 neutropenia lasting longer than 7 days, febrile grade 4 neutropenia requiring intravenous antibiotics, grade 4 thrombocytopenia, mucositis greater than grade 2 for more than 7 days, grade > or = 3 nonhematologic toxicity (excluding alopecia, vomiting, and muscular pain), no hematologic recovery on day 42 (for group 1) or on day 35 (for group 2), neurotoxicity above grade 2, and persistence of nonhematologic toxicity (excluding alopecia, nausea/vomiting, and musculoskeletal pain) grade > or = 2 at scheduled re-treatment. If any of the events occurred during the first cycle in three or more of six patients, maximum tolerated dose was considered to have been reached. The hematologic toxicity associated with the two treatment schedules was mainly neutropenia, but it was of short duration. Very few dose reductions or dose delays were necessary. Until now, the six planned courses have been administered without colony-stimulating factors. No toxic death has occurred. Grade 2 or 3 peripheral neuropathy has occurred in 12% of patients, mainly with high doses of paclitaxel. At this time, the maximum tolerated dose has not been reached at paclitaxel 275 mg/m2 every 4 weeks or 225 mg/m2 every 3 weeks, and enrollment continues.

Feasibility study of an alternating schedule of radiotherapy and chemotherapy in advanced uterine cervical carcinoma.

From July 1981 to April 1982, 36 patients with advanced cervical carcinoma stage III (24 patients) and stage IV (12 patients) entered a feasibility study of a radiotherapy and chemotherapy combination. The first three chemotherapy courses consisted of cis-platinum alone (50 mg/m2) and were interdigitated with radiotherapy. Six more courses composed of an association of cis-platinum (50 mg/m2) and cyclophosphamide (400 mg/m2) were given after the completion of radiotherapy. Radiotherapy was delivered in two courses of 25 Gy separated by a gap of 2 weeks. The overall 4-year survival rate was 35% (95% CI: 22%). The 4-year survival rate, cumulative loco-regional failure rate, and cumulative metastasis rate were respectively 44% (95% CI: 20%), 56% (95% CI: 21%), and 30% (95% CI: 21%) in stage III and 28% (95% CI: 27%), 83% (95% CI: 21%) and 74% (95% CI: 30%) in stage IV. The incidence of immediate and late complications was low: no patient had her radiotherapy stopped because of an intolerance and two patients had their chemotherapy stopped because of an haematological intolerance. Only one patient presented a severe late clinical complication (small bowel injury).

[Is the progesterone test a generalizable method of screening for neoplastic and preneoplastic lesions of the endometrium?]. / Le "test à la progestérone" est-il la méthode généralisable de dépistage des lésions néoplasiques et prénéoplasiques de l'endomètre?

A "progesterone test" has recently been proposed as a tentative method to detect early neoplastic and pre-neoplastic lesions of the uterus endometrium. At the time progesterone is stopped, a "deprivation" metrorragia demonstrates a remanent hyperoestrogenism, which represents a well-known risk factor for this type of lesion. The method has been evaluated in private practice; 389 patients were offered the test: 87% accepted. Metrorragias were observed in 28% of the cases; however, no neoplastic nor pre-neoplastic lesions could be detected in this group of patients. Moreover, one patient presented with an advanced endometrial cancer one year after a negative test. The reliability of such a test clearly needs further evaluation.

[Chemotherapy of cancers of the uterine cervix with a combination of bleomycin, mitomycin, cisplatin and etoposide]. / Chimiothérapie des cancers du col utérin par une association de bléomycine, mitomycine, cisplatine et étoposide.

Sixty patients with advanced carcinoma of the cervix were treated with 3-week cycles of chemotherapy consisting of bleomycin (10 mg/m2, D1, 2, 3), mitomycin (10 mg/m2, D1), cisplatin (80 mg/m2, D3), etoposide (100 mg/m2, D1, 2, 3). Twenty-six patients had prior therapy. Toxicities noted were primarily nausea, vomiting, asthenia, fever and myelosuppression, especially in the pre-treated patients. One patient died of pulmonary toxicity. Of the 34 untreated patients, 25 objective responses (74%) were observed, with two complete responses (6%) and among the 26 pre-treated patients, ten objective responses (39%) with only one complete response. The mean duration of response was 3.8 months [2-14]. These data indicate that combination chemotherapy regimen is active against advanced and recurrent cervical cancer but caution is required for administration and continuation of treatment after four cycles. This method of chemotherapy has significant potential for primary treatment in patients with locally advanced disease.

[Study of high doses of carboplatin as a first choice in the therapy of advanced ovarian cancers]. / Etude du carboplatine administré à forte dose en première ligne thérapeutique dans les cancers de l'ovaire évolués.

Thirty female patients with ovarian cancer of poor prognosis were included in a chemotherapy trial using high dose IV carboplatin--800 mg/m2 every 5 weeks. The subjects had three to six cycles prior to second laparotomy. Twenty-eight patients were assessable. There was no neurological, auditory or renal toxicity. Limiting toxicity was haematological, the mean neutrophil count was less than 650 mm3 and the mean platelet count less than 30,000/mm3. No death occurred from toxicity. The clinical response rate was 67%, and the surgical response rate 53.5%, with 15% complete histological responses. Survival at 18 months is 36%. A trial concerning 36 patients treated with an association of carboplatin at the same dose combined with cyclophosphamide has just been completed and the results are being analyzed.

[Randomized trial of initial chemotherapy in 151 locally advanced carcinoma of the cervix (T2b-N1, T3b, MO)]. / Essai randomisé de chimiothérapie initiale dans 151 carcinomes du col utérin localement étendus (T2b-N1, T3b, M0).

From 1982 to 1987, a randomized phase III trial was performed in order to determine the long-term effect of induction chemotherapy before standard pelvic irradiation in stage IIb-N1, III squamous cell carcinomas of the cervix. Patients were randomized to either chemotherapy and radiotherapy (C + R group) vs radiotherapy alone (R group). Radiotherapy for all patients consisted of 50 Gy in the pelvis with a boost by external irradiation or by brachytherapy (cumulative dose of 68 Gy). The chemotherapy regimen was an association of methotrexate (10 mg/m2, D2-4), chlorambucil (4 mg/m2, D1-5), vincristine (0,7 mg/m2, D1), cisplatin (80 mg/m2, D5), given every 3 wks; at least 2 courses were to be given before assessing efficacy and 2 more courses were given to patients who responded. One hundred and fifty-one patients were fully evaluable, after a mean follow-up of 38 mths (range 2-7 years), 76 in the R arm and 75 in the C + R arm. The response rate (greater than 50%) to chemotherapy was 42.5%. After completion of treatment, the complete response rate was 86.8% in the R arm and 86.3% in the C + R arm. The 3 year disease-free survival was 58.7% in the C + R group and 54.5% in the R group, and the median survival was 39.5% and 47 months respectively (NS). The survival of patients with a complete response at the end of radiotherapy was significantly better in the C + R group (when chemotherapy had been active) than in the R group (p = 0.04). Although radiotherapy was not modified whether patients had initial chemotherapy or not, tolerance was not significantly different between the 2 groups. The data collected in this study indicate that: 1) efficacy of induction chemotherapy is the only available predictive test for long-term results, 2) tolerance to treatment is crucial for optimal chemotherapy delivery, 3) higher dose intensity of chemotherapy in cervical carcinoma is associated with a better tumor reduction, and probably a better survival.

[Neoadjuvant chemotherapy of stage IIb or III cancers of the uterine cervix. Long-term results of a multicenter randomized trial of 151 patients]. / Chimiothérapie néoadjuvante des cancers du col utérin aux stades IIb et III. Résultats éloignés d'un essai randomisé pluricentrique portant sur 151 patients. Groupe coopérateur de gynécologie de la Fédération nationale des centres de lutte contre le cancer (FNCLCC).

Present chemotherapy, with cisplatin combinations, currently offers the possibility of seeking adjuvant therapy in locally advanced and bulky carcinomas of the cervix, which have an unfavorable prognosis (nodal involvement). This initial adjuvant chemotherapy may improve the results of classical pelvic irradiation. From 1982 to 1987, a randomized phase III trial was performed in order to determine the long term effect of induction chemotherapy before irradiation in stage IIb-N1, III, M0 squamous cell carcinomas of the cervix. Radiotherapy (R) for all patients consisted in 50 Gy in the pelvis with a boost by external irradiation of the brachytherapy (cumulative dose of 68 Gy). The chemotherapy regimen (C + R group) was an association of methotrexate, chlorambucil, vincristine and cisplatin, given every 3 weeks, at least two courses were to be given before assessing efficacy and two more courses were given to patients who responded. After a follow up of 5-10 years, 76 patients were fully evaluable in the R arm and 75 in the C + R arm. The response rate (> 50%) to chemotherapy was 42.5% and after completion of treatment, remission rate was 93% in the R arm and 96% in the C + R arm. The disease-free survival was 40% in the C + R group and 35% in the R group, and the median survival was 42 and 45 months respectively (NS). The survival of patients with a complete response at the end of radiotherapy was significantly better in the C + R group when they are responding to chemotherapy, than in R group (P < 0.05). Radiotherapy was not modified whether patients had an initial chemotherapy or not; tolerance was not significantly different between the two groups. Efficacy of induction chemotherapy is an available test for long term results. This approach has the potential for improving the outlook in patients with high-risk primary cancer: earlier use and higher dose intensity of chemotherapy may be associated with a better cytoreduction, and probably a better survival. Further controlled investigations are warranted to confirm the value of adjuvant chemotherapy in cervical cancer.

[Ovarian tumor with hepatoid differentiation. Discussion and review of the literature. Report of a case]. / Tumeur ovarienne avec différenciation hépatoïde. Discussion et revue de la littérature. A propos d'une observation.

One case of hepatoid carcinoma of the ovary is described, and a review of the literature is performed. This tumor is now considered as a variety of common epithelial tumor of the ovary and must be distinguished from other ovarian-neoplasms, especially from hepatoid yolk sac tumors.

[Para-aortic lymphadenectomy in the surgical evaluation of ovarian cancer]. / La lymphadénectomie para-aortique dans le bilan chirurgical des cancers de l'ovaire.

Lymph node involvement was demonstrated by para-aortic lymphadenectomy in 6 out of 20 women treated for ovarian cancer with macroscopically limited lesions at first and second-look laparotomy. When added to those reported in the literature, these results suggest that 20% of stages I and II ovarian cancers involve the lymph nodes, which considerably influences the prognosis and treatment of cancers otherwise considered as limited. We therefore suggest that biopsy of the lumbar aortic lymph nodes should be systematically performed in the surgical evaluation of ovarian cancers at an early stage.

[Adjuvant treatment of cystadenocarcinoma]. / Traitements adjuvants des cystadénocarcinomes.

Adjuvant therapy remains necessary for all ovarian cancers expanding outside the ovary, and should be adjusted to stage and persistent tumor burden. Many problems need precise answers. Although progresses have been made, results are still unsatisfactory. The need for multicentric studies and trials is utmost underlined.