RANDOMIZED CLINICAL-TRIALS AND OTHER APPROACHES IN CLINICAL RESEARCH

Authors
Citation
E. Frei, RANDOMIZED CLINICAL-TRIALS AND OTHER APPROACHES IN CLINICAL RESEARCH, Cancer, 74(9), 1994, pp. 2610-2613
Citations number
8
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CancerACNP
ISSN journal
0008-543X
Volume
74
Issue
9
Year of publication
1994
Supplement
S
Pages
2610 - 2613
Database
ISI
SICI code
0008-543X(1994)74:9<2610:RCAOAI>2.0.ZU;2-U
Abstract
Phase III randomized clinical trials have greatly contributed to our u nderstanding of the pathobiology of neoplastic disease and, particular ly, to therapeutic progress. However, randomized Phase III studies are no better than or are critically dependent on Phase I and Phase II st udies for positive therapeutic leads that are compelling enough to tes t in the Phase III arena. The variables involved in the series of rand omized trials that led to the curative treatment of acute lymphocytic leukemia also resulted in an understanding of the principles of cancer therapy in therapeutic research. These principles, when applied to Ho dgkin's disease in non-Hodgkin's lymphoma, testis cancer, childhood so lid tumors, and others, resulted in a substantial cure rate for those diseases. However, for the adult epithelial common solid tumors, a sec ond strategy, adjuvant chemotherapy, was required. This has resulted i n a 20% reduction in mortality in patients with node positive and node negative breast cancer. Tamoxifen has been similarly effective in pat ients with postmenopausal breast cancer. In colon cancer, adjuvant che motherapy with fluorouracil plus levamisole has decreased mortality to a comparable degree. New agents, modulations, combination chemotherap y, and biotherapeutics are being addressed to the adjuvant situation w hich has proven effective in a variety of neoplastic diseases. A third strategy is neoadjuvant chemotherapy. This involves the use of chemot herapy first for patients with solid tumors, designed to down-stage th e primary tumor, thus making it more susceptible to less radical surge ry and to organ- or limb-sparing procedures in osteogenetic sarcoma an d in head and neck cancer. For example, neoadjuvant chemotherapy has n ot resulted in an increased survival as compared with the appropriate control but has allowed for important quality-of-life contributions, s uch as limb-sparing and radical surgery-sparing procedures. In additio n to new agents and combination chemotherapy, dose is a critical varia ble. This is most evident clinically in the transplantation arena. Com parative studies recently completed, for example, in patients with adj uvant breast cancer and with acute leukemia indicate that dose is a si gnificant factor in tumor control.