Efficacy and tolerability of the ifosfamide-epirubicin combination in relapsed ovarian cancer.

A retrospective study evaluating the efficacy and tolerability of epirubicin-ifosfamide (EI) in patients with relapsed advanced ovarian cancer (ROC) after prior chemotherapy was conducted. A total of 93 patients received epirubicin (50 mg/m(2), day 1), ifosfamide (1500 or 2500 mg/m(2), days 1-3), and mesna monthly. Thirty-five percent had received one line of chemotherapy (platinum 100%, taxanes 8%); 38%, two lines; and 27%, more than two lines. Fifty-three percent received 2500 mg/m(2)/day ifosfamide and 47% received 1500 mg/m(2)/day ifosfamide. Ifosfamide was administered by continuous infusion in 12 patients. Mean number of courses was 4 (1-12). Grade 4 toxicity was 69% neutropenia and 12% thrombocytopenia. Three patients on high-dose ifosfamide as a short infusion had central nervous system dysfunction resulting in death. There were 84 assessable patients: 7 (8%), complete responses; 13 (15%), partial responses; and 20 (24%), stable disease. Median time to progression was 5 months (3 days to 36 months). The EI combination appears to be effective in ROC. However, toxicity with high-dose ifosfamide administered by short infusion is not acceptable. Tolerability can be improved using ifosfamide at 1500 mg/m(2) by continuous infusion. The combination of ifosfamide with newer anthracycline agents such as liposomal doxorubicin may be an alternative and needs further evaluation for use after first-line taxane-based chemotherapy.

Non-Hodgkin's lymphoma of the testis: a retrospective study of 84 patients treated in the French anticancer centres.

Primary non-Hodgkin's lymphoma of the testicle is rare. We analysed cases treated in French anticancer centres from 1969 to 1995. All cases were reviewed and classified according to the R.E.A.L. Classification. Eighty-four cases were included in this study. The median age was 67 years (17-85). Disease was classified as stages I in 42 cases, stages II in 19 and stages III-IV in 23. Diffuse large B-cell lymphoma was diagnosed in 75% of cases. Treatment included orchidectomy and radiotherapy and/or chemotherapy. A complete response was obtained in 72.6% of the patient population and in 100%, 68% and 33% of stage I, II and III-IV disease respectively. Recurrence occurred in 32 cases and the most frequent site was the central nervous system: six of these patients presented stage I disease. Median overall survival was 32 months for the entire population, 52 months for stage I, 32 months for stage II, and 12 months for stage III-IV cases (P < 0.0001). Among patients presenting stage I disease, no difference was found between those treated with combined surgery and chemotherapy or surgery followed or not followed by radiotherapy. This study confirms that non-Hodgkin's lymphoma of the testicle carries a poor prognosis. Systemic adjuvant chemotherapy should be discussed because of the high recurrence rate. Inclusion of these cases in large co-operative prospective studies is recommended.

Results of a phase III prospective, randomised trial, comparing mitoxantrone and vinorelbine (MV) in combination with standard FAC/FEC in front-line therapy of metastatic breast cancer.

This comparative phase III trial of mitoxantrone+vinorelbine (MV) versus 5-fluorouracil+cyclophosphamide+either doxorubicin or epirubicin (FAC/FEC) in the treatment of metastatic breast cancer was conducted to determine whether MV would produce equivalent efficacy, while resulting in an improved tolerance in relation to alopecia and nausea/vomiting. This multicentre study recruited and randomised 281 patients with metastatic breast cancer; 280 were evaluable for response survival and toxicity (138 received FAC/FEC, 142 received MV). Patient characteristics were matched in each arm and stratification for prior exposure to adjuvant therapy was made prospectively. The overall response rate (ORR) was equivalent in the two arms (33.3% for FAC/FEC versus 34.5% for MV), but MV was more effective in patients who had received prior adjuvant therapy (13% (95% confidence interval (CI) 3-23) for FAC/FEC versus 33% (95% CI 20-47) for MV P=0.025) with a better progression-free survival (PFS) (5 months (range 1-18 months) versus 8 months (range 1-27 months); P=0.0007 for FAC/FEC versus MV, respectively) while FAC/FEC was more effective in previously untreated patients (ORR 43% (95% CI 33-53) versus 35% (95% CI 25-45), P=0.26; PFS 9 months (range 0-29 months) versus 6 months (range 0-26 months) P=0.014). Toxicity was monitored through the initial six cycles of therapy; febrile neutropenia and delayed haematological recovery was more frequent for MV (P=0.001), while nausea/vomiting of grades 3-4 was greater for FAC/FEC (P=0.031), as was alopecia (P=0.0001), cardiotoxicity was the same for the two regimens. MV represents a chemotherapy combination with equivalent efficacy to standard FAC/FEC and improved results for patients who have previously received adjuvant chemotherapy. Toxicity must be balanced to allow for increased haematological suppression and risk of febrile neutropenia with MV compared with a higher risk of subjectively unpleasant side-effects such as nausea/vomiting and alopecia with FAC/FEC.

High-dose platinum versus standard dose in advanced ovarian carcinoma: a randomized trial from the Gynecologic Cooperative Group of the French Comprehensive Cancer Centers (FNCLCC).

OBJECTIVE: The aim of this study was to evaluate the impact of platinum dose intensity on pathological response rate and overall survival in patients with advanced ovarian adenocarcinoma. METHODS: Between February 1992 and December 1996, 195 previously untreated patients with FIGO stage IIb-c, IIIb-c, or IV with macroscopic residual disease after suboptimal debulking surgery were randomized to receive CCC (100 mg/m(2) of cisplatin, 300 mg/m(2) of cyclophosphamide, 300 mg/m(2) of carboplatin, n = 96) or CC (100 mg/m(2) of cisplatin, 600 mg/m(2) of cyclophosphamide, n = 99) for six courses at 28-day intervals. A second-look laparotomy was planned at the end of chemotherapy. RESULTS: In the CCC arm, the platinum compound received dose intensity and relative total dose were 85 and 76%; in the CC arm, they were 94 and 85%. Grade 3-4 toxicity was more frequent in the CCC arm than in the CC arm for leukopenia (56% vs 26%, P < 0.001), febrile neutropenia (18% vs 4%, P = 0.002), anemia (31% vs 5%, P < 0.001), thrombopenia (55% vs 4%, P < 0.001), and ototoxicity (8% vs 0%, P < 0.001). The pathologic complete response rate was 22 and 14% in the CCC and CC arms, respectively (P = 0.19). With a median follow-up of 53 months, the median time to failure and the 3-year treatment failure-free survival rate were 17.4 months and 22% vs 13 months and 11% in the two arms, respectively (P = 0.01). The median survival time and the 3-year overall survival rate were, respectively, 30 months and 42% vs 25 months and 33% (P < 0.20). CONCLUSION: The platinum dose intensification (1.6-fold increase) obtained with the CCC association improves the treatment failure-free survival without significant impact on overall survival when compared with the CC regimen in suboptimal debulked ovarian adenocarcinoma. However, because of its high rate of hematologic toxicity and ototoxicity, this association cannot be recommended for routine practice.

A multicenter phase II study with triptorelin (sustained-release LHRH agonist) in advanced or recurrent endometrial carcinoma: a French anticancer federation study.

The objective of this phase II multicenter study was to assess the efficacy and tolerance of triptorelin (a sustained-release LHRH agonist) in advanced or recurrent endometrial cancer. A total of 101 monthly intramuscular injections were administered to 24 eligible patients (median number/patient = 3; range 1-12). Mainly due to progression, only 16 patients received 3 or more injections. Among the 23 evaluable patients, 1 complete and 1 partial response (response rate of 8.7%) and 5 disease stabilizations were observed, often of long duration, but never in an irradiated area or after progestogens treatment failure. Median survival for eligible patients was 7.2 months (range: 1-36 months). Only grade 1 toxicities possibly related to the treatment were observed in 4 patients. In conclusion, triptorelin was safe, well tolerated, and easily manageable, and the very low toxicity did not impair the quality of life in these patients with a very poor prognosis. Although the response rate was disappointing, several patients showed early evidence of efficacy which may be of long duration. Response rates range between 0 and 45% in different published studies. Additional studies with stricter inclusion criteria and a larger sample size are necessary to better evaluate the role of LHRH agonists in endometrial adenocarcinomas.

[Carboplatin and etoposide combination for the treatment of recurrent epithelial ovarian cancer]. / Association de carboplatine et étoposide dans le traitement des rechutes des cancers épithéliaux de l'ovaire.

UNLABELLED: The objective of this phase II study was to determine the efficacy and toxicity of a combination of carboplatin and etoposide as salvage treatment, in previously treated patients with persistent or recurrent ovarian cancer following first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: From July 1990 to August 1994, 58 patients were treated with 3-week cycles of chemotherapy consisting of carboplatin (200 mg/m2, D1) and etoposide (120 mg/m2, D1, D2). Criteria for evaluating previous response to cisplatin were strictly defined. RESULTS: The overall response rate was 36%, with five complete responses (CR, 9%), 16 partial responses (PR, 27%) and the median duration of response was 10 months (range: 4 to 38). In the group of patients who progressed during the first year following the diagnosis, the response was 1 CR and 2 PR (12%) and in the group of patients who progressed from the second year after diagnosis, 4 CR and 14 PR (56%), with a median survival of 8.5 and 21 months respectively (p = 0.0013). The response rate was 59% in the potentially platinum sensitive group versus 8.7% in the primary resistant group (0.02 < p < 0.05). Myelotoxicity was the main side-effect but did not appear to be cumulative. Grade 3 and grade 4 anemia were observed in 26% and 3% of the patients respectively, neutropenia in 14% and 2% and thrombocytopenia in 14% and 8.5%. One patient died of sepsis associated with neutropenia. CONCLUSION: Treatment was easily manageable and well tolerated. The advantage of carboplatin and etoposide combination in potentially responsive patients is represented by the reduced nephrotoxicity, neurotoxicity and ototoxicity as compared with cisplatin containing regimen, with durable feasibility in outpatients. This second-line chemotherapy for ovarian cancer is effective as salvage treatment in potentially responsive patients with late recurrent tumors, while paclitaxel is the drug of choice for patients who have developped primary or secondary resistance to platin therapy.

Interstitial brachytherapy for penile carcinoma: a multicentric survey (259 patients).

Although cancer of the penis is a rare disease, we have collected 506 cases through a multicentric study. In the present study we analyse the results obtained from 259 patients treated by interstitial brachytherapy from 1959 to 1989. Among the 259 patients, 184 males had exclusive brachytherapy (group A) while 75 received a combination of surgery and brachytherapy and/or external beam irradiation (EBI) (group B). Five- and 10-year survival rates are, respectively: overall survival, 66 and 52%; cause-specific survival, 88 and 88%; disease-free survival, 78 and 67%. One hundred and forty-three patients in group A (78%) and 48 (64%) in group B avoided mutilation of the penis while late side effects occurred in 137/259 patients (53%). Survival depends on the volume of the tumor and the presence of involved nodes; systematic groin dissection does not however seem advisable.

Phase II trial of intraperitoneal carboplatin in ovarian carcinoma patients with macroscopic residual disease at second-look laparotomy. A multicentre study of the French Fédération Nationale des Centres de Lutte Contre le Cancer.

BACKGROUND: Because of its antitumour activity and its pharmacological advantage when administered by the intraperitoneal route, carboplatin was studied in a phase II multicentric trial. The aim of the study was to determine the response rate and the toxicity of carboplatin administered intraperitoneally and to determine if pathological complete response could be attained in women with macroscopic residual ovarian cancer at second-look laparotomy after intravenous cisplatin chemotherapy. PATIENTS AND METHODS: Twenty-nine patients with macroscopical residual disease after intravenous cisplatin-based chemotherapy at second-look laparotomy, were treated at that time with 300 mg/m2 of carboplatin administered in the abdominal cavity every four weeks for six cycles. In instances of negative findings at physical and CT scan examination, laparotomy evaluation was performed and the catheter was removed. The dose of carboplatin was increased or decreased according to hematological toxicity. RESULTS: Efficacy is evaluable in 25 pts: 2 pts had pathological complete responses and 1 pt had microscopic disease (12% response rate of evaluable patients). Toxicity is evaluable for 135 cycles in 29 patients. No grade 4 hematological toxicity was observed, 2 pts had grade 3 leukopenia and 3 pts had grade 3 thrombocytopenia; grade 3 vomiting was observed in 11% of cycles. No peritoneal complication was observed; catheter dysfunction occurred after the first cycle in one patient who refused a surgical procedure to remove the catheter and to pursue treatment. CONCLUSION: Intraperitoneal carboplatin demonstrates efficacy in patients with macroscopical residual disease at second-look laparotomy after first-line cisplatin chemotherapy. The recommended dose for further studies is 300 mg/m2 administered every 4 weeks. A low response rate does not favour a randomised study.

[CA 15.3 and early diagnosis of recurrence in breast cancer]. / CA 15.3 et diagnostic précoce de récidive dans les cancers du sein.

This retrospective study shows the advantage of the CA 15.3 assay for the early detection of relapse in breast cancer. It involved 473 women with invasive canalar carcinoma who had local recurrence or metastasis and/or an elevation of CA 15.3 (> 35 kU/l). The positive predictive value is excellent (97.7%). Sensitivity is poor for local relapse (13.7%), but a marker elevation at this time is a good prognostic factor of further distant metastasis (88%). It is better in the case of distant metastasis (74%), especially in bone and and liver localizations. CA 15.3 measurement at two month intervals may allow an early detection in 40% of distant metastasis. These results confirm the need of trials to test the benefits in terms of survival of early treatment of breast cancer metastasis only proved by CA 15.3 elevation, without any clinical or radiological finding.

Quality of life in long-term survivors of nonseminomatous germ cell testicular tumors.

A total of 109 survivors of curative therapy for nonseminomatous germ cell testicular tumor was interviewed an average of 9 years after treatment to assess long-term physical, emotional and sexual sequelae. An age-matched group of healthy men were interviewed similarly as controls. Of the physical sequelae loss of ejaculation was prominent (30% of the patients) and appeared directly related to retroperitoneal lymph node dissection surgery (p < 0.01). Hypofertility was apparent among patients during the posttreatment period compared to controls (p < 0.01). Other physical complications were present in 35% of the patients and 8% were severe. Laparotomy was associated with incisional hernia and radiotherapy with gastrointestinal complications (p < 0.001). Psychoemotional status was similar among patients and controls before cancer diagnosis but 60% of the patients had obvious emotional problems during the treatment period, which were more severe in those who had a history of such problems. Anxiety, often with insomnia, affected 49% of the patients, while irritability and depression were noted in 34%. At the interview 30% of the patients versus 5% of the controls had psychoemotional dysfunction (p < 0.001) but half of the affected patients had a history of problems preexisting the diagnosis of cancer. Sexual complaints were encountered in 19% of the patients before cancer diagnosis compared to only 7% of the controls (p < 0.02). During cancer therapy 57% of the patients had sexual symptoms, primarily loss of erection and decreased frequency of intercourse. Residual problems were more prevalent among patients (38%) than controls (11%, p < 0.001). Sexual impairment was associated with direct treatment effects and persisted more often when symptoms developed during the treatment period. Although direct treatment related effects should decrease with modern single modality therapy, appropriate attention should be placed on counseling to help avoid long-term psychoemotional and sexual complications of the disease process and its treatment.

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.

[Malignant thymoma. Apropos of 10 cases]. / Thymomes malins. A propos de 10 cas.

The current article proposes a review of the literature on the malignant thymoma, from 10 cases treated in the Henri Becquerel's Centre in Rouen. The middle age varies between 45 and 55 years, the sex ratio is 1/1. The principal histological type is the lympho-epithelial, then épithelial and lymphocytic. The 5-year survival varies between 45 and 75%. The most important factor of prognosis is the invading's degree. The initial treatment is surgical with an excision as complete as possible, then X-ray treatment. The utilization of the chemotherapy is still undecided, the cisplatin is the most effective product.