[Advanced renal carcinomas with special situations. How to treat them?]. / Cancers du rein avancés en situations particulières. Comment les traiter ?

Advanced or metastatic renal carcinoma represents a frequent disease in oncologic practice. Few years ago, in immunotherapy era, treatments had quickly reached deadlock. New therapies targeting vascular endothelial growth factors and their receptors (VEGF-R), sorafenib, sunitinib and bevacizumab, and the mammalian target of rapamycin (mTOR), temsirolimus and everolimus, have modified these patients prognosis and their quality of life in a few years. Nevertheless, patients included in randomized trials presented severe inclusion criteria. Then in the daily practice, patients have distinctive characteristics which were not evaluated in large pivotal studies: poor performance status, older patients, renal dysfunction, cerebral metastases or non clear cell renal cancer. In published trials, a few data concerning these situations are reported, and these studies have often included small samples, were retrospective or not randomised. However compared to global population, tolerance have not been very different in geriatric patients, or patients with poor performance status, or with central neurological metastases, or with papillary and chromophobe sub-types. On the contrary progression free or overall survivals increases are more difficult to confirm. Also before starting treatment, ratio between potential benefit and possible toxicities have to be evaluated. In patients with renal insufficiency, VEGF receptor inhibitors seem to be cautiously initiated at reduced doses, and to be increased according to tolerance. Due to these poor proof levels, clinical trials are needed for these specific populations.

Cytotoxicity of iridals, triterpenoids from Iris, on human tumor cell lines A2780 and K562.

Six different triterpenoids (known iridals) extracted from Iris germanica L. were purified and bioassayed on two cultured human tumor cell lines: A2780 and K562 (and for each one a drug-sensitive and a drug-resistant cell line). All of the tested iridals had an IC50 in the 0.1 to 5.3 microg/ml range. Some of them were shown to be more effective than doxorubicine. Toxicity of iridals on multi-drug resistance (MDR) expressing cell lines seemed to indicate that the effects of these triterpenoids are less affected by MDR than those of doxorubicine or taxol.

Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-naive patients and patients pretreated with fluorouracil-based chemotherapy.

PURPOSE: To assess the efficacy of irinotecan (CPT-11) in the treatment of advanced colorectal cancer in both chemotherapy-naive and pretreated patients. PATIENTS AND METHODS: Two hundred thirteen patients (aged 18 to 75 years) with metastatic colorectal cancer, World Health Organization (WHO) performance status < or = 2, and life expectancy > or = 3 months were treated with CPT-11 350 mg/m2 every 3 weeks. All 178 patients eligible for efficacy analysis had not received more than one prior fluorouracil (5-FU)-based chemotherapy regimen (adjuvant or palliative) and had adequate hematologic, renal, and hepatic function. RESULTS: Primary tumor sites were the colon (71%) and rectum (28%). Sixty-six percent of the patients had > or = two metastatic sites. Ninety-eight percent of the patients had undergone previous surgery, and 77.5% had received prior chemotherapy. Thirty-two of 178 eligible patients achieved on objective response (four complete responses [CRs] and 28 partial responses [PRs]; response rate, 18%; 95% confidence interval, 12.6% to 24.4%), 65 were stable, and 59 progressed. The response rate was 17.7% in the pretreated group and 18.8% in the chemotherapy-naive group. Within the former subgroup, response rates of 16.1% were reported in patients who were progressive on prior 5-FU chemotherapy and 19.1% in patients who were progressive off such treatment. The median duration of objective response (9.1 months) and median time to achievement of a response (9.3 weeks) did not differ between chemotherapy-naive and pretreated patients. The most frequent adverse events were neutropenia, which developed in 80% of the patients, delayed diarrhea (87%), alopecia (88%), fatigue (81%), and nausea/vomiting (77%). All these adverse events were manageable. Severe (WHO grade 3 or 4) neutropenia was only observed in 18% of the cycles, leukopenia in 11%, delayed diarrhea in 11%, and nausea and vomiting in 3%. Development of simultaneous grade 3 or 4 neutropenia and delayed diarrhea during 4% of the cycles was the safety issue of greatest concern. CONCLUSION: CPT-11 has definite activity in the treatment of advanced metastatic colorectal cancer both in chemotherapy-naive and in pretreated patients who experienced disease progression on 5-FU, which suggests a lack of cross-resistance between CPT-11 and 5-FU. Diarrhea and neutropenia, the major toxicities of CPT-11, contribute to the risk to develop febrile neutropenic sepsis.

Penile cancer chemotherapy: twelve years' experience at Institut Gustave-Roussy.

Between 1980 and 1992, 14 patients (median age 50 years) with penile carcinoma were treated with multidrug combination chemotherapy in our institution. Twelve patients had Stage IV (Jackson classification) tumor, 1 patient each had Stage III and Stage II. All patients received cisplatin-based chemotherapy. Cisplatin was associated with either 5-fluorouracil (4 patients), methotrexate and bleomycin (4 patients), methotrexate (3 patients), Adriamycin (1 patient), bleomycin and vinblastine (1 patient), or bleomycin and epirubicin (1 patient). Thirteen patients were evaluable for response. Objective response was encountered in 2 patients (15%) with 1 complete response and 1 partial response. Response duration was difficult to determine because of additive radio-therapy or patient was lost to follow-up. There were 2 patients with long-term evidence of no disease among 12 patients with Stage IV disease. These 2 patients received complementary irradiation in association with the chemotherapy. The response rate was dismal in our series. Methotrexate-based regimens seem to be the most active. The bimodality treatment with multidrug chemotherapy and radiotherapy for advanced penile cancer could offer a survival advantage in the management of these patients.