LE Magazine March 2002
Page 2 of 2
Lissoni's (1999) researchers report anecdotal evidence that the patients receiving melatonin experience a relief of anxiety, improved quality of life and overall improvements in patient function and well-being. They also report that melatonin diminishes blood cell damage induced by conventional radiotherapy and chemotherapy. Moreover, they report that melatonin forestalls weight loss in patients with advanced disease.
Melatonin has been shown effective in inducing sleep in healthy subjects. Melatonin is recognized to have a hypnotic effect at pharmacologic doses and causes an increased propensity to sleep, as demonstrated in placebo-controlled clinical trials. Published studies have found that ingestion of melatonin increases the speed of falling asleep, the duration of sleep and the quality of sleep (Dawson and Encel, 1993; Zhdanova et al., 1995).
Melatonin may have an effect on mood. Depression is a common problem in patients with advanced cancer. Patients with depression (as are patients with advanced cancer) are found to have low nighttime serum melatonin concentrations (Brown et al., 1987). Because many cancer patients have disruptive sleep patterns and experience depression, melatonin's role as a supportive agent requires further investigation.
|Table 1. Lissoni's Phase II Randomized Clinical Trial Results|
|TumorType ||Patient Number ||Comparison ||Melatonin Dose ||One Year Survival ||Level Of Significance|
|Metastatic Non Small Cell Lung ||63 ||Supportive Care Only ||10 mg ||26% ||Under 1% ||<0.05|
|Glioblastoma ||30 ||Conventional Radiotherapy ||10 mg ||43% ||Under 1% ||<0.05|
|Metastatic Breast ||40 ||Tamoxifen ||20 mg ||63% ||24% ||<0.01|
|Brain Metastases ||50 ||Conventional Radiotherapy ||20 mg ||38% ||12% ||<0.05|
|Metastatic Colorectal ||50 ||IL-2 ||40 mg ||36% ||12% ||<0.05|
|Metastatic Non Small Cell Lung ||60 ||IL-2 ||40 mg ||45% ||19% ||<0.05|
The need for further research on melatonin therapy in cancer
We still have relatively little understanding of how melatonin works in the human body. Many questions have been raised, but few have been answered. The long-term effects of chronic melatonin use are currently unknown.
Despite the broad public interest in melatonin and other complementary therapies, there is only modest funding for clinical investigations in melatonin research. American and European governments finance some basic research on melatonin, yet, very little funds have been allocated to investigate the clinical implications of melatonin therapy in the management of chronic disease.
|Cancer researchers at CTCA are hoping to confirm and significantly extend Lissoni's most interesting findings in a large-scale multi-center trial conducted in the United States.|
These issues have compelled investigators at Cancer Treatment Centers of America (CTCA) to develop cancer trials that address the most critical issues involving melatonin's use in cancer patients. In doing so, CTCA has also partnered with two renowned experts in the field of melatonin therapy and chronobiology, David E. Blask, MD, PhD from the Bassett Research Institute at Mary Imogene Bassett Hospital and William JM Hrushesky, MD of the University of South Carolina School of Medicine, respectively. Interestingly, Dr. Blask was the discoverer of melatonin's role in breast cancer, and Dr. Hrushesky has made major discoveries in applying the science of chronobiology to cancer treatment.
Currently, most of the data on the benefits of melatonin on cancer patients comes from Lissoni's center in Italy. These researchers have steadily produced results showing that melatonin has a role in cancer therapy. The trials in Italy have been small, but nonetheless, produced provocative results. These studies involved small numbers of patients and collected insufficient high quality data on a variety of clinical issues to measure melatonin's true benefits in cancer. For these reasons, the medical community does not accept the Lissoni's data as definitive. Cancer researchers at CTCA are hoping to confirm and significantly extend Lissoni's most interesting findings in a large-scale multi-center trial conducted in the United States.
Investigators at CTCA have addressed the design shortcomings found in the literature with several innovations. First, the study is investigating whether the circadian activity/rest rhythms in cancer patients is normal or abnormal prior to melatonin therapy. Surprisingly, this will be the first trial ever to investigate: (1) whether cancer patients produce a nocturnal pulse of melatonin prior to therapy, and (2) what fraction of patients with advanced cancer suffer abnormalities in their circadian activity/rest rhythm. This information will provide physicians and researchers with insight on why patients are unable to complete or respond to therapy.
Second, CTCA is investigating the therapeutic dose of melatonin required to induce its known biological effects in cancer patients undergoing chemotherapy. Consequently, physicians will know whether the patient was exposed to a biologically effective dose of melatonin. These findings will also be the first to report on the absorption and degradation of oral melatonin in patients undergoing chemotherapy.
Third, CTCA is looking at melatonin's therapeutic benefits at two distinct phases of the circadian cycle-diurnal and nocturnal. Lissoni's group investigated nocturnal doses of melatonin, while Gonzalez's group in Colorado had patients take melatonin every four hours (a non-chronobiologic dosing pattern).
Finally, investigators at CTCA are using validated instruments that accurately measure health-related quality of life, sleep quality and fatigue in patients undergoing melatonin treatment with chemotherapy.
If melatonin lives up to its promise, cancer treatment will be drastically improved by reduced treatment-related toxicity, improved quality of life and increased long-term survival. This exciting research will also provide the necessary clues on melatonin's role as an effective anti-aging therapy in humans.
|For more information about Cancer Treatment Centers of America's integrative care, call Oncology Information Specialist, Doug White at 1-800-577-1255.|
Purchase Melatonin from the Life Exetnsion Foundation
Brzezinski, A., (1997). Melatonin in humans. New England Journal of Medicine 336, 186-194.
Cagnacci A, Krauchi K, Worz-Justice A, Volpe A (1997). Homeostatic versus circadian effects of melatonin on core body temperature in humans. J Biol Rhythms 12, 319-367.
Dawson D, Encel N (1993). Melatonin and sleep in humans. J Pineal Res 15, 1-12.
Gonzalez, R., Sanchez, A., Ferguson, J., Balmer, C., Daniel, C., Cohn, A., & Robinson, W. (1991). Melatonin therapy of advanced human malignant melanoma. Melanoma Research 1, 237-243.
Greaves M (2000). Cancer: The Evolutionary Legacy. Oxford University Press, Oxford United Kingdom.
Hruskesky WJM (2001). Melatonin Cancer Therapy. Pgs 476-508, "In The Pineal Gland and Cancer." Eds. Bartsch C, Bartsch H, Blask DE, Cardinali DP, Hrushesky WJM, Mecke D. Springer Berlin.
Kloeden PE, Rossler R, Rossler OE (1994). Artificial life extension; the epigenetic approach. Ann New York Academy of Science 719, 474-482.
Kloeden PE, Rossler OE, Rossler R (1990). A predictive model for life expectancy curves. Biosystems 24, 119-125.
Latif, AZB, Signorini D, Gregor A, Grant R, Ironside JW, Whittle IR (1998). Application of the MRC brain tumour prognostic index to patients with malignant glioma not managed in randomised control trial. J Neurol Neurosurg Psychiatry 64: 747-750.
Lerner A, Case J, Takahashi Y, Lee T, Mori W (1958). Isolation of melatonin, the pineal gland factor that lightens melanocytes. J Am Chem Soc 80: 2587.
Lissoni P, Barni S, Ardizzoia A, Paolorossi F, Crispino S, Tancini G, et.al. (1992). Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin. Oncology 49, 336-9.
Lissoni P, Barni S, Ardizzoia A, Tancini G, Conti A, Maestroni G. (1994). A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasms. Cancer 73, 699-701.
Lissoni, P., Barni, S., Meregalli, S., Fossati, V., Cazzaniga, M., Esposti, D., & Tancini, G. (1995). Modulation of cancer endocrine therapy by melatonin: a phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progressing under tamoxifen alone. British Journal of Cancer 71, 854-856.
Lissoni, P., Pittalis, S., Rovelli, F., Vigore, L.., Roselli, MG., Brivio, F. (1995). Interleukin2, melatonin and interleukin-12 as a possible neuroimmune combination in the biotherapy of cancer. J. Biol. Regul. Heomeost. Agents 9, 63-69.
Lissoni P, Barni S, Tancini G, Ardizzoia A, Ricci G, Aldeghi R, et.al. (1994). A randomized study with subcutaneous low-dose interleukin 2 alone vs. interleukin 2 plus the pineal neurohormone melatonin in advanced solid neoplasms other than renal cancer and melanoma. Br J Cancer 69, 196-9.
Lissoni, P., Meregalli, S., Nosetto, L., Barni, S., Tancini, G., Fossati, V., Mestroni, G. (1996). Increased survival time in brain glioblastomas by a radioneuroendocrine strategy with radiotherapy plus melatonin compared to radiotherapy alone. Oncology 53, 43-46.
Lissoni, P., Paolorossi, F., Ardizzoia, A., Barni, S., Chilelli, M., Mancuso, M., Tancini, G., Conti, A., & Maestroni, G.J.M. (1997). A randomized study of chemotherapy with crisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state. Journal of Pineal Research 23, 15-19.
Lissoni P, Paolorossi F, Tancini G, Barni S, Ardizzoia A, Brivio F, et al. (1996). Is there a role for melatonin in the treatment of neoplastic cachexia? Eur J Cancer 32A, 1340-3.
Lissoni P. (1998). Melatonin and cancer treatment. In Ed Watson RR. Melatonin In the Promotion of Health. CRC Press Boca Raton.
Lissoni, P., Barni, S., Mandala, M., Ardizzoia A., Paolorossi, F., Vaghi, M., Longarini, R., Malugani, F., and Tancini, G. (1999). Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 12, 1688-1692.
Maestroni G, Conti A, Pierpaoli, W (1988). Pineal melatonin, its fundamental role in aging and cancer. Annals of the New York Academy of Sciences 521, 140-148.
Maestroni, G. (1993). The immunoneuroendrocrine role of melatonin. J Pineal Res 14, 1-10.
Olcese J (1999). Melatonin After Four Decades. Adv Exp Med and Biol., 460 1-473. ed J Olcese.
Olshansky SJ, Carnes BA (2001). The Quest For Immortality; Science At The Frontiers Of Aging. Pgs 254 W. w. Norton, New York, New York.
Third Stromboli Conference on Aging and Cancer; The Aging Clock, The Pineal Gland and other Pacemakers in the Progression of Aging and Carcinogenesis. Annals of the New York Academy of Sciences 719, pg587 eds, Pierpaoli W, Regelson W, Fabris N.
Zhdanova I, Wurtman R, Lynch H (1995). Sleep-inducing effects of low doses of melatonin ingested in the evening. Clin Pharmacol Ther 57, 552-558.
Purchase Melatonin from the Life Exetnsion Foundation
Back to the Magazine Forum