[Antineoplastic protocols: between effectiveness and adverse effects].
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
E Lucchi
Publications and source records attributed to E Lucchi.
Preclinical development of camptothecin derivatives and clinical trials in pediatric oncology.
Although the prognosis of childhood cancers has dramatically improved over the last three decades, new active drugs are needed. Camptothecins represent a very attractive new class of anticancer drugs to develop in paediatric oncology. The preclinical and clinical development of two of these DNA-topoisomerase I inhibitors, i.e. topotecan and irinotecan, is ongoing in paediatric malignancies. Here we review the currently available results of this evaluation. Topotecan proved to be active against several paediatric tumour xenografts. In paediatric phase I studies exploring several administration schedules, myelosuppression was dose-limiting. The preliminary results of topotecan evaluation in phase II study showed antitumour activity in neuroblastoma (response rate: 15% at relapse and 37% in newly diagnosed patients with disseminated disease) and in metastatic rhabdomyosarcoma (40% in untreated patients). Topotecan-containing drug combinations are currently investigated. Irinotecan displayed a broad spectrum of activity in paediatric solid tumour xenografts, including rhabdo-myosarcoma, neuroblastoma, peripheral primitive neuroectodermal tumour, medulloblastoma, ependymoma, malignant glioma and juvenile colon cancer. For several of these histology types, tumour-free survivors have been observed among animals bearing an advanced-stage tumour at time of treatment. The clinical evaluation of irinotecan in children is ongoing. Irinotecan undergoes a complex in vivo biotransformation involving several enzyme systems, such as carboxylesterase, UDPGT and cytochrome P450, in children as well as in adults. Preclinical studies of both drugs have shown that their activity was schedule-dependent. The optimal schedule of administration is an issue that needs to be addressed in children. In conclusion, the preliminary results of the paediatric evaluation of camptothecin derivatives show very encouraging results in childhood malignancies. The potential place of camptothecins in the treatment of paediatric malignant tumours is discussed.
Animals↗
[Epithelial ovarian cancers (advanced stage)].
Ovarian carcinomas are known to have a poor prognosis, not only because their diagnosis is often made in late time, but the risk of recurrence after initial treatment is high. This overview was made to explain the different approaches while dealing with a patient with an ovarian carcinoma. A particular interest went to the familial history of ovarian cancer, concerning a very short population, as shown in the recent data. Prognostic factors, the way of diagnosis, and the histologic classification were also explained in detail. Ovarian cancer is more often found out at an advanced stage of the disease, that's the reason why the treatment of epithelial ovarian cancer was extensively studied, with the recent approaches of the new drugs; for instance, the use of combinations with taxoides in the first part of treatment, or a numerous of other agents, particularly at the time of the recurrence, like the camptothecines, the gemcitabine, or the new derivatives of platinum. The management of the patient after initial treatment (follow up, maintenance therapy) were also included in this overview. As for the "borderline" tumors, a peculiar chapter was devoted to them.
Antineoplastic Agents↗
Bimonthly high dose leucovorin and 5-fluorouracil 48-hour infusion with interferon-alpha-2a in patients with advanced colorectal carcinoma. Groupe d'Etude et de Recherche sur les Cancers de l'Ovaire et Digestifs (GERCOD).
UNLABELLED: BACKGROUND; The rationale for the modulation of 5-fluorouracil (5-FU) with interferon-alpha (IFN) is inhibition of 5-FU catabolism and 5-FU resistance. Clinical trials have shown debatable results when IFN is given in high doses with 5-FU used as a bolus alone or in combination with leucovorin (LV). A first-line Phase II study was performed in 50 patients with metastatic colorectal carcinoma who were given a bimonthly combination of high dose LV, a high dose 48-hour infusion of 5-FU, and a low dose of IFN. METHODS: The regimen was comprised of a 2-hour infusion of LV, 500 mg/m2, on each of 2 consecutive days, and a 48-hour infusion of 5-FU, 1.5 to 2 g/m2/24 hours, starting after Day 1 of LV treatment every 2 weeks until there was evidence of disease progression. IFN was administered subcutaneously three times weekly at a dose of 3 MU (body surface area [BSA] < 1.75 m2) or 4.5 MU (BSA > OR = 1.75 m2). RESULTS: World Health Organization toxicity Grade 3-4 occurred in 21 patients (42%): diarrhea in 6%, mucositis in 12%, neutropenia in 30%, and alopecia in 8%. The overall response rate was 44%; 1 patient had a complete response (2%), 21 had partial responses (42%), 23 had stable disease (46%), and 5 had disease progression (10%). The median progression free survival was 9 months, and median survival was 25 months. CONCLUSIONS: Bimonthly high dose LV, a high dose 48-hour infusion of 5-FU, and a low dose of IFN had good activity in patients with advanced colorectal carcinoma. However, as in other schedules of LV and 5-FU, IFN induces high grade toxicity.
Adenocarcinoma↗