Recent advances in the treatment of AIDS-related Kaposi's sarcoma.

Kaposi's sarcoma (KS) is the most common malignancy associated with HIV infection and is considered an AIDS defining condition by the US Centers of Disease Control Guidelines. Several advances in the treatment of AIDS-related KS have been achieved over the past few years, even though a gold standard therapy for KS has not yet been defined and treatment must be tailored to individual needs. Since the availability of highly active antiretroviral therapy (HAART), a dramatic clinical response has been documented in patients with KS, making HAART an essential approach in the management of KS in most, if not all, patients with AIDS-related KS. However, in case of aggressive, visceral, and/or life-threatening KS, more complex therapeutic schedules have to be taken into account, including chemotherapy, radiotherapy, and/or immunotherapy. In general, systemic treatment for KS is limited to widespread, symptomatic disease, whereas local interventions are indicated for minimal, cosmetically troublesome lesions. Among new cytotoxic agents, liposomal anthracyclines and paclitaxel are highly effective molecules for KS and have been approved by the US Food and Drug Administration (FDA) as first-line and second-line monotherapy, respectively, for advanced KS. Furthermore, a greater understanding of the pathogenesis of KS has lead to the development of an array of new experimental agents. Many antiangiogenic agents such as AGM 1470 (TNP 470), thalidomide, and glufanide disodium (IM 862) have produced encouraging responses in patients with KS and large clinical trials are in progress. Retinoic acids may also block neoangiogenesis as well as proliferation of KS cells in vitro, and they have been used either systemically or topically with a high response rate. Thus, a topical compound 0.1% alitretinoin gel was approved in 1999 by the FDA for the treatment of skin lesions associated with KS. Human chorionic gonadotropin, a hormonal agent, has shown a strong inhibitory activity in KS cells, but its role in the regression of KS lesions is not clear. Finally, the identification of a novel gamma-herpesvirus, human herpesvirus-8, as a causative agent for KS, together with novel antiangiogenic compounds, such as metalloproteinase inhibitors, may offer promising targets for the therapy of KS.

Stanford V regimen plus consolidative radiotherapy is an effective therapeutic program for bulky or advanced-stage Hodgkin's disease.

Since September 1996, 48 untreated patients with bulky or advanced-stage Hodgkin's disease received the 12-week Stanford V chemotherapy regimen followed by consolidation radiotherapy at a dose of 36 Gy to bulky mediastinal disease and 30.6 Gy to the initial sites of disease > or =3 cm in transverse diameter. After the combined therapy, 46 of 48 (96%) achieved complete remissions. With a median follow-up of 48 months, the 5-year overall survival was 95% and freedom from progression 86%. There were no treatment-related deaths. All but one premenopausal female patient (who received pelvic and inguinal irradiation) recovered normal menses. Until now no case of secondary leukemia or myelodysplasia was observed. Our results confirm that the Stanford V regimen with consolidation radiotherapy is safe and effective in patients with bulky or advanced-stage Hodgkin's disease, achieving very high remission and overall 5-year survival rates. Longer follow-up is necessary to evaluate the extent of all complications.

Gemcitabine combined with carboplatin in patients with malignant pleural mesothelioma: a multicentric phase II study.

BACKGROUND: Malignant pleural mesothelioma (MPM) is increasing rapidly worldwide. Currently, pemetrexed plus cisplatin chemotherapy showed a survival advantage versus cisplatin alone. No impact on patient survival of surgery, radiotherapy, or their combination has been demonstrated. METHODS: Eight centers in northeastern Italy participated in a Phase II multicenter study. Chemotherapy was comprised of carboplatin area under the concentration-time curve 5 on Day 1 and gemcitabine 1000 mg/m(2) on Days 1, 8, and 15. This cycle was repeated every 4 weeks. RESULTS: Between July 1996 and September 2000, 50 patients were treated. Of the sample, 68% were males, 88% had a Eastern Cooperative Oncology Group performance status score of 0-1, 56% had Stage I-II disease, 68% had epithelioid histology, and 62% had no previous treatments. The delivered dose intensity of gemcitabine was 617 mg/m(2) per week, which was 82% of the planned dose (750 mg/m(2) per week). For carboplatin, the delivered dose intensity was 80 mg/m(2) per week. Overall, 44% of 15th day doses were omitted or reduced. Twenty-six percent of the patients had partial responses (95% confidence interval: 15-40%) and 24% had disease progression. None of the patients had complete responses. The median response duration was 55 weeks (range, 13-113 weeks). Patients had good clinical benefit. For example, 46% had improved dyspnea, 40% improved in weight, and 26% experienced pain reduction. Patients developed Grade 3-4 leukopenia during 18 cycles (11%) of chemotherapy. Grade 3-4 thrombocytopenia occurred more frequently, i.e., there were 24 episodes (15%) among 17 patients. Grade 3 anemia developed among patients during eight cycles (5%). None of the patients developed Grade 3-4 nonhematologic toxicity. The median survival of this sample of patients was 66 weeks with 53%, 30%, and 20% of patients alive at 1, 2, and 3 years, respectively. The median progression-free survival period was 40 weeks. CONCLUSIONS: The gemcitabine/carboplatin combination is a valid option in the treatment of MPM due to its acceptable toxicity profile, the good response rate, and the clinical benefit to patients. Minor adjustments in schedule (3-week cycles instead of 4-week cycles) would permit a more optimal treatment administration.