Annals of oncology : official journal of the European Society for Medical Oncology
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Up to now, the majority of adjuvant chemotherapy trials in gastric cancer have failed to show a clear survival benefit as compared to surgical controls, and this is especially true for trials conducted in western countries. But this does not necessarily mean, that adjuvant chemotherapy of gastric cancer is in general ineffective. There are several common threads that appear repeatedly in adjuvant therapy trials which might help to explain the current situation. ⋯ There are sufficient data, that in comparison to 'limited' surgery, extended surgery with systematic lymphadenectomy of the N2 compartment markedly improves the prognosis of patients with stage II and IIIa tumors. The kind of chemotherapy, its timing and scheduling, and route of administration might also have been inappropriate to demonstrate a possible benefit of adjuvant therapy. All these things have to be considered seriously in future well designed trials, if an assumed therapeutic gain is to be demonstrated by adjuvant treatment of gastric cancer.
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Controversy still exists over the optimal management of early-stage Hodgkin's disease (HD); presentation features may have a different prognostic impact according to initial therapy, and long-term toxicity must be fully evaluated. ⋯ In stage IA-IIA HD, the combined modality therapy reduced the risk of relapse compared to radiation alone; long-term toxicity of RT was not negligible and relapses could occur late.
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356 children below 16 yrs of age with CS/PS IA, IB, and IIA were treated in the studies HD-78, HD-82, HD-85, HD-87, and OEPA-pilot 87 between June 1978 and Sept 1990. All patients received combined modality treatment (CMT) with 2 courses of chemotherapy (CT). In HD-78 and HD-82, the MOPP-derived drug combination OPPA (ADR instead of mechlorethamine) was applied. Extended-field radiotherapy (RT) was given in HD-78 using 36-40 Gy to involved-fields (IF) and 36-40 Gy vs. 18-20 Gy to adjacent fields. In HD-82 only IF-RT was applied using 35 Gy. When gonadotoxic effects of procarbazine (PC) in boys was detected in follow-up examinations, this drug was eliminated in studies HD-85 and HD-87 (OPA). Dosages of IF-RT were 35 Gy in HD-85 and 30 Gy in HD-87. With HD-87 a simultaneous pilot study was initiated to test the new combination OEPA (E = etoposide) together with 25 Gy IF-RT. ⋯ 2 OPPA plus IF-RT using < 30 Gy can presently be considered optimal therapy for girls with localized HD. 2 OEPA plus 25 Gy IF-RT are being evaluated for boys in a phase III study (HD-90). In summary, there are good reasons to use CMT in early stages of HD in children, provided a highly effective CT of short duration and low long-term toxicity with low-dose IFI is applied.
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The conventional phase I clinical trial stands as a bridge between the laboratory and the clinic in the development of novel anticancer agents. The purpose of the phase I study is primarily to determine toxicity and to define the maximum tolerated dose of the drug in man. It is assumed for this purpose that dose-response curves for toxicity and efficacy are parallel or, simply expressed, the more pain, the more gain. Novel antineoplastic drugs are being developed that are mechanistically remote from conventional cytotoxic drugs, which have DNA as their predominant target; some of these new agents have, at least in vitro, bell-shaped dose-response curves. ⋯ It is essential that flexible clinical trial methodologies are developed to accommodate new drugs and that attempts are made, when possible, to incorporate pharmacodynamic endpoints in addition to toxicological endpoints.