A phase II trial of high-dose chemotherapy (HDCT) supported by hematopoietic stem-cell transplantation (HSCT) in germ-cell tumors (GCTs) patients failing cisplatin-based chemotherapy: the Multicentric TAXIF II study.

BACKGROUND: High-dose chemotherapy (HDCT) is an effective salvage treatment of germ-cell tumors (GCTs) patients. In the first salvage setting, 30%-70% of patients may achieve durable remissions. Even when HDCT is administered as subsequent salvage treatment, up to 20% of patients may still be definitively cured. However, patients with refractory/relapsed disease still have a very poor long-term prognosis, requiring earlier intervention of HDCT. PATIENTS AND METHODS: This phase II trial was addressed to nonrefractory patients failing Cisplatin-based chemotherapy. Inclusion criteria included seminomatous GCT in relapse after two lines of chemotherapy, nonseminomatous GCT in relapse after first or second lines, partial remission after first line, primary mediastinal GCT in first relapse. Patients received two cycles combining Epirubicin and Paclitaxel (Epi-Tax), followed by three consecutive HDCT, one using a Paclitaxel/Thiotepa (Thio-Tax) association and two using the 5-day Ifosfamide-Carboplatin-Etoposide regimen. The main objective was to determine the complete response rate. RESULTS: Forty-five patients were included between September 2004 and December 2007: 44 received the first HDCT cycle, 39 two HDCT cycles, 29 could receive the whole protocol. Sixteen patients did not receive the entire protocol, including eight (17.7%) for toxic side-effects. Two patients (4.4%) died of toxicities, and 17 (37.7%) of disease progression. With a median follow-up time of 26 months (range, 4-51), the final overall response rate was 48.8% (including a complete response rate of 15.5% and a partial response/negative serum markers rate of 26.6%) in an intent-to-treat analysis. The median progression-free survival (PFS) and overall survival (OS) times were 22 months [95% confidence interval (CI) 2-not reached] and 32 months (95% CI 4-49), respectively. The 2-year PFS was a plateau setup at 50% (95% CI 32-67) and the 2-year OS was 66% (95% CI 44-81). CONCLUSION: The TAXIF II protocol was effective in nonrefractory GCT patients failing Cisplatin-based chemotherapy. The toxic death rate remained acceptable in the field of HDCT regimens. TRIAL REGISTRATION NUMBER: NCT00231582.

[Androgen deprivation therapy for prostate cancer and osteoporotic risk]. / Suppression androgénique dans le cancer de la prostate et risque ostéoporotique.

Androgen deprivation therapy represents an important part of the management of prostate cancer. However, epidemiological data have shown that it is a well-established cause of osteoporosis and increased risk of fracture. So far no consensus guidelines have been published regarding the screening and treatment of osteoporosis in men with prostate cancer. Here we report the design of a new questionnaire, derived from the FRAX(®) ("Fracture Risk Assessment Tool") algorithm, to evaluate the risk of fracture in those patients. In accordance with recent reviews and on the basis of their experience, our French board of experts recommends systematic screening for osteoporosis with dual energy x- ray absorptiometry scans, practice of exercise and calcium and vitamin D supplementation, and selective treatment with bisphosphonates in men at greatest osteoporotic risk.

Experimental studies and preliminary clinical trial of vinorelbine-loaded polymeric bioresorbable implants for the local treatment of solid tumors.

Vinorelbine is a new 5' nor Vinca alkaloid, active by i.v. route, in various types of cancer disease such as non-small cell lung cancer and advanced breast cancer. In order to evaluate the possibility of using this drug for local treatment of cancer, Vinorelbine-loaded bioresorbable polymeric implants were prepared using a copolymer of D,L-lactic and glycolic acids (PLA 37.5 GA 25). According to the manufacturing process, the 1.2-mm-diameter cylindrical rods obtained had a drug content of 1, 5, or 20% (w/w) and released half of their content within about 6 days in vitro. In vivo release in rats was slower, half of the drug being released after about 14 days. A dose-dependent antitumoral effect was observed in mice (solid P388 leukemia model) when implants were administered into or in contact with the tumor. At highest drug loads and when administered soon after tumor implantation, Vinorelbine implants were more effective than i.v. administration (median survival time of treated animals related to untreated controls, greater than 360 versus 188). In dogs, results of toxicity experiments revealed that administration of implants in vital organs must be avoided. On the contrary, s.c. administration was well tolerated. A transient local necrosis was observed in the days following implantation, but normal skin was recovered after about 10 weeks. Thus, a clinical trial was conducted on patients with head and neck cancer; implantation of 20% loaded polymeric implants into the tumor sites succeeded in 8 of 9 patients. The sole failure was attributed to the unusual hardness of the tumor tissue. Except for a local transient inflammatory reaction (easily treated with nonsteroidal antiinflammatory agents), no other sign of toxicity was detected, and patients tolerated the device well. Fourteen days after implantation, patients underwent their planned surgery, and the implants were recovered. Residual drug content varied from 24 to 55%. In all cases, there was a clearly delimited necrotic area around the implant, ranging from 0.5 to 3.5 cm in diameter. In the smallest tumors, necrosis was also observed in the normal tissue inside this area. These results invite further studies to evaluate such drug-loaded polymeric implants.

Cytokines in metastatic renal cell carcinoma: is it useful to switch to interleukin-2 or interferon after failure of a first treatment? Groupe Français d'Immunothérape.

PURPOSE: Interleukin-2 (IL-2) and interferon alfa-2a (IFNalpha2a) have some antitumor activity in metastatic renal cell carcinoma either alone or in combination. To determine whether either of these cytokines might be efficient after failure of the other, we analyzed a series of patients treated with either IL-2 or IFNalpha2a as second-line treatment after failure of the other cytokine. PATIENTS AND METHODS: We recently performed a large multicenter study to determine the respective efficacy of IL-2, IFNalpha2a, or combined treatment in renal cell carcinoma. In this study, patients who progressed on the single-arm treatment could receive the other cytokine in a cross-over trial. IL-2 was administered as a continuous intravenous infusion for 5 days (18 x 10(6) IU/m(2)/d), and IFNalpha2a was administered three times weekly at 18 x 10(6) IU. RESULTS: A total of 113 patients with progressive disease after first-line treatment received either IFNalpha2a (n = 48) or IL-2 (n = 65). Toxicity during second-line treatment was similar to that observed during first-line treatment. Only four partial responses were observed (one with IFNalpha2a and three with IL-2). All partial responders had a performance status of 0 and lung metastases. Moreover, three of these four patients had stable disease or had responded to first-line therapy. Only one patient with confirmed disease progression after receiving IL-2 subsequently responded to IFNalpha2a. CONCLUSION: Cross-over after failure of IL-2 or IFNalpha2a is poorly efficient in metastatic renal cell carcinoma, especially when progression has been clearly documented.

Treatment of patients with metastatic renal carcinoma with a combination of subcutaneous interleukin-2 and interferon alfa with or without fluorouracil. Groupe Français d'Immunothérapie, Fédération Nationale des Centres de Lutte Contre le Cancer.

PURPOSE: Subcutaneous recombinant interleukin-2 (rIL-2) and recombinant interferon alfa-2a (rIFNalpha-2a) have been used extensively in the treatment of metastatic renal cancer. Most results, coming from noncontrolled phase II trials, showed inconsistent rates of response. More recently, the addition of fluorouracil (FU) was proposed to improve the efficacy of these regimens. PATIENTS AND METHODS: The role of a subcutaneous combination of rIL-2 and rIFNalpha-2a with or without FU was investigated. Patients were randomly assigned to receive a combination of rIL-2 and rIFNalpha-2a at weeks 1, 3, 5, and 7 or the same combination together with a continuous infusion of FU at weeks 1 and 5. The major end points of this multicenter, randomized trial were progression-free survival, response rate, and toxicity. Overall survival was a secondary end point. Tumor responses were reviewed by an independent committee. Analysis of the results was performed on an intention-to-treat basis. RESULTS: One hundred thirty-one patients were enrolled. There was no difference in toxicity between the arms, and no toxic death was observed. One partial response was observed in arm A and five in arm B. Progression-free survival did not differ between the arms, and rates at 1 year were 12% and 15% in arms A and B, respectively. No statistically significant differences were detected in any end point. CONCLUSION: The subcutaneous combination of rIL-2 and rIFNalpha-2a with or without FU does not benefit patients with metastatic renal carcinoma. Neither of these regimens can be recommended as standard treatment. The results of the subcutaneous cytokine regimen seem disappointing.

Subcutaneous interleukin-2, interferon alfa-2a, and continuous infusion of fluorouracil in metastatic renal cell carcinoma: a multicenter phase II trial. Groupe Français d'Immunothérapie.

PURPOSE: A phase II trial was designed to determine the efficacy and the tolerance of interleukin-2 (IL-2), interferon alfa-2a (IFNalpha), and fluorouracil (5-FU) in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: One hundred eleven patients were included. Patients received subcutaneous IL-2 9 x 10(6) IU daily for 6 days and IFNalpha 6 x 10(6) IU on days 1, 3, and 5 every other week for 8 weeks. 5-FU was administered through a continuous infusion at 600 mg/m2 for 5 consecutive days for 1 week every 4 weeks. RESULTS: The response rate was 1.8% (95% confidence interval [CI], 0% to 4.3%) with only two partial responses (PRs). Toxicity was moderate with 3.6% grade 4 events and two deaths related to treatment. CONCLUSION: This regimen of IL-2, IFNalpha, and 5-FU in patients with metastatic renal cell carcinoma was ineffective. The results raise the question of the dose and schedule of subcutaneous cytokines that must be used in metastatic renal carcinoma.

A national survey to determine prevalence of Trypanosoma cruzi infection among pregnant women in Ecuador.

A nationwide survey was conducted to obtain an estimate of Chagas disease prevalence among pregnant women in Ecuador. As part of a national probability sample, 5,420 women seeking care for delivery or miscarriage at 15 healthcare facilities were recruited into the study. A small minority of participants reported knowing about Chagas disease or recognized the vector. A national seroprevalence of 0.1% (95% confidence interval [95% CI] = 0.0-0.2%) was found; cases were concentrated in the coastal region (seroprevalence = 0.2%; 95% CI = 0.0-0.4%). No cases of transmission to neonates were identified in the sample. Seropositive participants were referred to the National Chagas Program for evaluation and treatment. Additional studies are necessary to determine if areas of higher prevalence exist in well-known endemic provinces and guide the development of a national strategy for elimination of mother-to-child transmission of Chagas disease in Ecuador.

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.

Evaluation of toxicity and efficacy of 186Re-hydroxyethylidene diphosphonate in patients with painful bone metastases of prostate or breast cancer.

UNLABELLED: Twenty-eight patients (12 men with prostate cancer, 16 women with breast cancer) were included in a phase II trial to evaluate the efficacy of 186Re-hydroxyethylidene diphosphonate (HEDP) on pain from bone metastasis and the toxicity of this agent. METHODS: After intravenous administration of 1295 MBq 186Re-HEDP, the efficacy was evaluated by means of a daily log. RESULTS: We observed an objective response in 67% of prostate cancer patients and in 36% of breast cancer patients. The mean duration of response was 45 d for prostate cancer patients and 24 d for breast cancer patients. No major adverse effects were observed. Marrow toxicity did not exceed grade 2 for white blood cells and grade 3 for platelets using National Cancer Institute criteria. CONCLUSION: 186Re-HEDP provides safe symptomatic relief of pain in prostate cancer patients. The benefit of this treatment is less clear in breast cancer patients. Further studies should be conducted to evaluate treatment by 186Re-HEDP at an earlier stage of the disease.

A randomized double-blind study evaluating Anandron associated with orchiectomy in stage D prostate cancer.

A randomized double-blind study with a 3-yr follow-up comparing the two arms "orchiectomy + Anandron (300 mg)" vs "orchiectomy + placebo" in 125 patients with stage D prostate cancer has confirmed the beneficial effects of the combined Anandron therapy on subjective parameters and on the best objective response (NPCP criteria), although these effects were not statistically significant, but failed to detect any improvement in time-to-disease progression or survival. Comparison with the results of other trials emphasizes the urgent need to establish suitable prognostic factors by further clinical research before evaluating the benefits of individual drugs.

Platinum concentration in human tumors of head and neck, uterine cervix, and breast following treatment with cisplatin.

Intratumoral platinum concentrations were measured in three tumor sites (head and neck, uterine cervix, and breast) 48 h after cisplatin administration according to the same protocol. The platinum levels were in the same order of magnitude in all tumors, but the concentration in breast tumors was found to be higher than that in tumors of the head and neck and of the uterine cervix.

Rapidly recycled, intensive alternating chemotherapy in heavily pretreated progressive nonseminomatous germ cell tumors a feasibility study.

To evaluate the feasibility and the efficacy of an intensive alternating chemotherapy regimen with hematopoietic growth factor support in the late salvage treatment of patients with metastatic nonseminomatous germ cell tumors (NSGCT), 14 patients with refractory or recurrent disease were treated with a combination regimen of vinblastine and bleomycin (VB) followed by three weekly cycles of BOP (bleomycin + vincristine + cisplatin) and subsequent CISCA (cyclophosphamide + doxorubicin + cisplatin) cycles. All patients experienced a grade 3 or 4 neutropenia despite prophylactic growth factor support; II patients required empiric antimicrobial therapy during the chemotherapy program. No toxic death or other significant adverse effect was seen. Eight patients achieved a complete remission and three patients had a partial remission with normalization of serum tumor markers at completion of chemotherapy. Four patients received high-dose chemotherapy with autologous bone marrow transplantation as consolidation therapy and one patient underwent a salvage surgery. Three patients remain free of disease at over 18, 26, and 36 months after therapy. We demonstrate here the feasibility of an intensive alternating chemotherapy schedule in the late salvage treatment of progressive NSGCT. Our results also suggest that the combination of such an approach with high-dose chemotherapy (HDCT) and/or surgery can be used in a curative attempt after the failure of first line salvage therapy.

Significance of PSA and PAP in patients with or without prostatic cancer.

Coupled prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) measurements (using the radioimmunoassay method) were carried out on 220 controls, 33 patients with prostatic hyperplasia, and 71 with carcinoma. The mean PSA value was 3.70 +/- 3.31 ng in the controls. A level of 10 ng was adopted as the upper limit of normal. Four of the eight cases of prostatic hyperplasia with a high PSA level (between 10 and 25 ng) underwent surgery. Histological tests confirmed benign hyperplasia. In the localized cancers, the PSA level was normal. In the metastatic cancers, PSA proved to be more sensitive than PAP. Thus, PSA is of little use in the early diagnosis of cancer; its systematic measurement as a means of cancer screening for the general public may even be misleading.

[Cancer of the prostate: therapeutic strategy in 1985]. / Cancer de la prostate: la stratégie thérapeutique en 1985.

After extensive staging, localized prostate carcinomas are treated by radical prostatectomy, external beam radiation therapy or interstitial radioactive implantation therapy combined or not with external radiation. For these patients, it is not demonstrated that adjuvant hormonotherapy increases survival duration. For metastatic carcinomas, orchiectomy or low dose of DES are possible. When carcinoma patients escape to endocrine treatment, there are given chemotherapy. Hormonal associations with central and peripheral action mechanisms could modify, in early future, present treatment options for advanced carcinomas.

[Spermatocytic seminoma. Apropos of 4 cases]. / Les séminomes spermatocytaires. A propos de 4 observations.

The records of 4 patients treated for a spermatocytic seminoma between 1974 and 1993 were reviewed. We described pathological and clinical features of this entity of seminoma which differs from those of classic seminoma. Spermatocytic seminoma is an essentially non metastasizing neoplasm unless complicated by the rare development of a sarcomatous component or metastatic spread.

[Unusual development of nonseminomatous germ cell tumors of the testis (NSGCT)]. / Evolution inhabituelle de tumeurs germinales non séminomateuses du testicule (TGNS).

The authors describe a clinical case of metastatic testicular non-seminomatous germinal tumor with several recurrences treated by the association of chemotherapy and surgery for remaining lesions. Based on this case a review of the literature is done to illustrate the evolution of treatments, to highlight the evolutive potential of mature teratoma, the delayed recurrences.

Comparison of platinum concentrations in human head and neck tumours following administration of carboplatin, iproplatin or cisplatin.

Tumour tissue levels of platinum were determined in patients with head and neck tumours receiving carboplatin (11 patients, 400 mg/m2) and iproplatin (5 patients, 360 mg/m2). The platinum concentrations ranged from 1.1 +/- 0.4 ng Pt/mg tissue (iproplatin administration) to 1.4 +/- 0.3 ng Pt/mg tissue (carboplatin administration). These results were compared with published platinum levels after cisplatin administration. Although the administered dose of carboplatin (1.08 mmol/m2) and iproplatin (0.86 mmol/m2) was higher than the cisplatin one (0.33 mmol/m2), no significant statistical differences were observed in the resulting platinum tissue levels. The constancy of tumour platinum level after treatment with different platinum complexes could be explained, at least for carboplatin and cisplatin, by both the tumour diffusion properties and the reactivity of the drugs.

[Karyotype of peripheral blood lymphocytes in patients treated for Hodgkin disease]. / Le caryotype des lymphocytes sanguins périphériques des hodgkiniens traités.

Peripheral lymphocyte chromosomes were analyzed in 55 consecutive patients with complete remission after treatment for Hodgkin's disease. In 8 patients, observed metaphases were too few in number. The other 47 patients, 29 men and 18 women, had been off all therapy for 53 months (median 41, ext. 1 to 250 months). The mean interval since the diagnosis was 78 months (median: 73 months) and the mean age at the time of chromosome analysis was 38 years (median: 34, ext. 10-78 years). No patient had either a preleukemic syndrome or leukemia. In contrast to karyotypes in normal controls and previously untreated patients, abnormal cells, hypodiploid, hyperdiploid and tetradiploid cells were more frequent. But neither monosomy 5 or 7 nor trisomy 8 were observed. Intrachromosomal rearrangements (gaps, breaks...) were significantly more frequent (12% vs 5% in untreated patients) particularly on chromosomes 1 and 2. Interchromosomal rearrangements were also numerous (1,25%) but no cells showed any specific translocation for malignant hemopathy. Chromosomal aberrations do not seem closely associated with treatments but influenced by the post-diagnosis interval and the factors present at the time of primary treatment.

[Cancer of the upper aerodigestive tract. Global study of 2418 cases]. / Les cancers des voies aérodigestives supérieures. Etude globale de 2418 dossiers.

The authors present the general results of a retrospective study on 2418 patients treated between 1976 and 1980. Primaries were located on buccopharynx in 51% of cases, pharyngolarynx in 45% and nasopharynx or nasal and paranasal cavities in 4%. Two out of 3 tumours were classified T3 T4 (UICC 1979) and 1 out of 2 patients presented with palpable cervical lymph nodes. Taking into account persistent diseases and recurrences, failure at primary sites occurred in 40% of patients, in the neck in 20%, distant metastases in 10%. Synchronous and/or metachronous cancers were observed in 1 out of 3 patients. Actuarial survival rates were 2/3 at 1 year, 1/3 at 3 years, 1/4 at 5 years and 1/7 at 8 years. Endolaryngeal tumours had the best prognosis while hypopharyngeal tumours had the worst prognosis.

[Imaging of testicular tumors]. / Imagerie des tumeurs du testicule.

Testicular cancer is the most common malignancy in young men and its incidence is increasing. The overall rate of cure can exceed 90% when management is optimal. Ultrasonography for diagnosis and thoraco-abdominal CT for staging are the optimal imaging modalities. In this paper we analyze technical parameters as well as findings and the strategy of examinations in testicular neoplasm.