- J Clin Oncol. 2006 Jan 1;24(1):136-40.
Unconventional anticancer agents: a systematic review of clinical trials.
Vickers AJ, Kuo J, Cassileth BR.
Medicine Service and Department of Epidemiology and Biostatistics,
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
PURPOSE: A substantial
number of cancer patients turn to treatments other than those
recommended by mainstream oncologists in an effort to sustain tumor
remission or halt the spread of cancer. These unconventional approaches
include botanicals, high-dose nutritional supplementation, off-label
pharmaceuticals, and animal products. The objective of this study was
to review systematically the methodologies applied in clinical trials
of unconventional treatments specifically for cancer.
1966 to 2005 was searched using approximately 200 different medical
subject heading terms (eg, alternative medicine) and free text words
(eg, laetrile). We sought prospective clinical trials of unconventional
treatments in cancer patients, excluding studies with only symptom
control or nonclinical (eg, immune) end points. Trial data were
extracted by two reviewers using a standardized protocol.
identified 14,735 articles, of which 214, describing 198 different
clinical trials, were included. Twenty trials were phase I, three were
phase I and II, 70 were phase II, and 105 were phase III. Approximately
half of the trials investigated fungal products, 20% investigated other
botanicals, 10% investigated vitamins and supplements, and 10%
investigated off-label pharmaceuticals. Only eight of the phase I
trials were dose-finding trials, and a mere 20% of phase II trials
reported a statistical design. Of the 27 different agents tested in
phase III, only one agent had a prior dose-finding trial, and only for
three agents was the definitive study initiated after the publication
of phase II data.
CONCLUSION: Unconventional cancer treatments have not
been subject to appropriate early-phase trial development. Future
research on unconventional therapies should involve dose-finding and
phase II studies to determine the suitability of definitive trials.