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.

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.

[Pleuro-pulmonary metastases from a malignant mesothelioma of the tunica vaginalis]. / Métastases pleuropulmonaires d'un mésothéliome de la vaginale testiculaire.

INTRODUCTION: Mesothelioma is a malignant tumour of the serous membranes that principally affects the pleura. Peritoneal, pericardial and tunica vaginalis mesothelioma are very rare. CASE REPORT: We report the case of a 65-year-old male with malignant mesothelioma of the tunica vaginalis (MTV). He presented with several local recurrences and, five years after the initial surgery, with pulmonary nodules and a pleural effusion. Pleural biopsies confirmed epithelioid mesothelioma. A diagnosis of pleuro-pulmonary metastases from previous malignant MTV was made. CONCLUSIONS: Malignant MTV is a rare and aggressive tumor with frequent local recurrences and, rarely, visceral metastases. This case report emphasizes the difficulties of the differential diagnosis between pleural mesothelioma and pleural metastases from MTV. The lack of any treatment for metastatic malignant MTV is discussed.

Refining the optimal chemotherapy regimen for good-risk metastatic nonseminomatous germ-cell tumors: a randomized trial of the Genito-Urinary Group of the French Federation of Cancer Centers (GETUG T93BP).

BACKGROUND: High cure rates are expected in good-risk metastatic nonseminomatous germ-cell tumor (NSGCT) patients with bleomycin, etoposide and cisplatin. PATIENTS AND METHODS: Patients received either three cycles of BE500P or four cycles of E500P every 3 weeks. Disease was defined according to the Institut Gustave Roussy prognostic model. Patients were retrospectively assigned into the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. A sample size of 250 patients was necessary for an expected favorable response rate (primary end point) of 90% and not more than a 10% difference between the two arms. RESULTS: Among 257 assessable patients, 124 and 122 patients achieved a favorable response in the 3BE500P and 4E500P arms, respectively (P = 0.34). Median follow-up was 53 months. The 4-year event-free survival rates were 91% and 86%, respectively (P = 0.135). The 4-year overall survival rates were not significantly different [five deaths versus 12 deaths, respectively (P = 0.096)]. Similar nonsignificant trends were observed in good IGCCCG prognosis patients. CONCLUSIONS: Both regimens produced similar results in terms of favorable response rates. As the trial was underpowered for survival analyses, conclusive data would require a larger randomized trial. Unless such a study is done, 3BE500P is the treatment of choice for metastatic NSGCT patients.

Sequential high-dose chemotherapy protocol for relapsed poor prognosis germ cell tumors combining two mobilization and cytoreductive treatments followed by three high-dose chemotherapy regimens supported by autologous stem cell transplantation. Results of the phase II multicentric TAXIF trial.

BACKGROUND: High-dose chemotherapy (HD-CT) is able to circumvent platinum resistance of resistant/refractory germ-cell tumors (GCTs), but expectancy of cure remains low. New strategies are needed with new drugs and a sequential approach. MATERIALS AND METHODS: Patients with relapsed poor-prognosis GCTs were scheduled to receive two cycles combining epirubicin and paclitaxel (Taxol) followed by three consecutive HD-CT supported by stem cell transplantation [one course combining cyclophosphamide, 3 g/m(2) + thiotepa, 400 mg/m(2), followed by two ICE regimens (ifosfamide, 10 g/m(2), carboplatin, AUC 20, etoposide, 1500 mg/m(2))]. RESULTS: From March 1998 to September 2001 (median follow-up, 31.8 months), 45 patients (median age, 28 years) were enrolled in this phase II study. Twenty-two patients received the complete course. Twenty-five patients died from progression and five from toxicity. The overall response rate was 37.7%, including an 8.9% complete response rate. The median overall survival was 11.8 months. The 3-year survival and progression-free survival rate was 23.5%. The 'Beyer' prognostic score predicted the outcome after HD-CT. CONCLUSION: Although our results warrant further studies on HD-CT in relapsed poor prognosis GCTs, patients with a Beyer score >2 did not benefit from this approach and should not be enrolled in HD-CT trials. Better selection criteria have to be fulfilled in forthcoming studies.

[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.

Phase II study of vinorelbine in patients with androgen-independent prostate cancer.

PURPOSE: To evaluate the efficacy and toxicity of vinorelbine in a phase II study in patients with progressive metastatic androgen-independent prostate cancer. PATIENTS AND METHODS: Forty-seven men with progressive metastatic prostate cancer refractory to first-line or second-line hormonal therapy were treated with vinorelbine, a semisynthetic vinca-alkaloid. Vinorelbine was given, on an outpatient schedule, at 25 mg/m2 weekly for at least eight weeks or until progression or excessive toxicity. RESULTS: Forty-seven patients were included in the study, 33 being evaluable for tumour response, 36 for response to PSA, 21 for clinical benefit and 45 for toxicity. Median actual weekly dose was 19 mg/m2 (range 12.0-26.2 mg/m2). Six of thirty-six patients (17%) demonstrated a biologic response with a 50% or more decline in serum PSA on two consecutive measurements taken at least two weeks apart. The median duration of biologic response was 2.7 months. Two of three patients with measurable disease obtained an objective response but remained unconfirmed. No change disease was reported in 23 patients (49%). On entry into the study, 30 patients had symptomatic bone pain and required narcotic or non-narcotic analgesics. Clinical benefit from vinorelbine was achieved in 15 patients out of 21 (32% of the intent to treat analysis population and 71% of the assessable patients). Due to the low number of questionnaires (QLQ-C30) filled in, it was insufficient to allow any statistical analysis. The median survival was 10.2 months. Toxicity was mainly haematologic with 51% of patients experiencing grade 3 or 4 granulocytopenia. Three patients developed deep vein thrombosis. Non-haematologic toxicity, mainly nausea and neurotoxicity, was mild. CONCLUSION: The administration of weekly vinorelbine appears to be a safe treatment for those patients with androgen-independent prostate cancer and poor prognosis features who require chemotherapy. These results provide data for future investigation of vinorelbine in combination regimens.

Extraperitoneal laparoscopic para-aortic lymph node dissection for early stage nonseminomatous germ cell tumors of the testis with introduction of a nerve sparing technique: description and results.

PURPOSE: The extraperitoneal approach is well suited to urological surgery. Transperitoneal laparoscopic para-aortic lymph node dissection has been reported with good results for early stage nonseminomatous germ cell tumor of the testis. We report our current experience with laparoscopic para-aortic lymph node dissection using a new extraperitoneal approach. MATERIALS AND METHODS: The technique consists of an internal iliac extraperitoneal approach and complete unilateral modified laparoscopic para-aortic lymph node dissection. We assessed 25 patients with clinical stage I (20) or IIA (5) testicular nonseminomatous germ cell tumor who underwent this technique, including left and right lymphadenectomy in 13 and 12, respectively. In addition, nerve sparing dissection was performed in the last 12 cases. RESULTS: An average of 9.8 (range 3 to 19) and 17. 7 (range 5 to 29) lymph nodes were dissected on the right and left sides, respectively. No intraoperative or postoperative complications developed that required laparotomy. Average operative time was 3 hours 50 minutes (range 3 to 5 hours). Average hospital stay was 1.2 days (range 1 to 3). Results were positive in 10 patients who were given platinum based chemotherapy. At close followup of 15 months no late adverse effects or recurrence was observed. CONCLUSIONS: Although a larger experience and longer followup are required, extraperitoneal laparoscopy is a safe, effective and well suited method of diagnostic para-aortic lymph node dissection for early stage testicular nonseminomatous germ cell tumor. The specific advantages of this approach are no blind trocar insertion or bowel contact and ability to perform nerve sparing dissection. Moreover, it is cost-effective since only 3 trocars are necessary and recovery is rapid.

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.

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.

[Laparoscopic lumbo-aortic lymphadenectomy in early-stage non-seminomatous germ cell tumors of the testis: Why? How?]. / Le curage lombo-aortique laparoscopique dans les tumeurs germinales non séminomateuses (TGNS) du testicule aux stades précoces: pourquoi? Comment?

OBJECTIVES: Laparoscopic lumbo-aortic lymphadenectomy is proposed in order to decrease the morbidity of pretreatment lymph node dissections for early stage NSGCT of the testis. Two approaches are presented and compared retrospectively: the transperitoneal approach and the extraperitoneal approach. MATERIAL AND METHODS: From 1991 to 1999, 57 patients with clinical stage I (50) to IIA (7) NSGCT underwent pretreatment laparoscopic investigation of the para-aortic lymph nodes: 32 transumbilical transperitoneal dissections and 25 internal iliac extraperitoneal dissections were performed. RESULTS: Only the 19 patients with lymph node invasion received chemotherapy. All serious complications occurred in the transperitoneal group: 1 case of chylous ascites and 2 cases of transient neurological complications, 2 cases of permanent ejaculation failure and 2 extranodal recurrences among the 38 pN0 patients. CONCLUSIONS: Laparoscopy, especially extraperitoneal, appears to be a safe, effective and appropriate modality for pretreatment lumbo-aortic lymph node evaluation in early stage NSGCT of the testis.

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.

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.

The diagnostic value of urinary Crosslaps and serum alkaline phosphatase in patients with prostate cancer.

OBJECTIVE: To determine whether the urinary excretion of Crosslaps and serum alkaline phosphatase (ALP) are useful bone markers in patients with prostate cancer. PATIENTS AND METHODS: The study included 112 patients, comprising 25 with benign prostatic hyperplasia and 87 with carcinoma of the prostate, 41 of whom had localized prostate cancer and 46 with bone metastases. In the last group, 16 were stable and 30 were in clinical progression. Prostate-specific antigen (PSA) and the bone markers serum bone ALP and urinary Crosslaps were determined on the same day. RESULTS: The rates of excretion of Crosslaps were significantly greater in patients with than in those without bone metastases. Only Crosslaps showed a significant difference between patients with stabilized metastatic disease and those with no bone involvement. Crosslaps had a higher specificity and positive predictive value than had PSA level in patients with bone metastases, and a higher sensitivity than bone ALP. CONCLUSION: These preliminary findings suggest that Crosslaps may be useful as an additional bone marker in patients with prostate cancer and may provide information of the metastatic spread to bone in these patients. Prospective studies with serial measurements of bone markers are currently underway to relate these results to the progression of disease and to evaluate the response to treatment of bone metastases.

[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.

[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.

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.

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.

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.