A Phase I and pharmacokinetic study of high dose tamoxifen and weekly cisplatin in patients with metastatic melanoma

Abstract

or regression was documented, the patients received a second 3-week cycle of 2 Department of Medicine, University of Califor-DDP and were then reevaluated for response. Patients with progressive disease nia-San Diego, La Jolla, California.were removed from the study. 3 Department of Pharmaceutical Sciences, Med- RESULTS.In 25 consecutive patients, the overall response rate was 20%. No reical University of South Carolina, Charleston, sponses were observed in patients treated with TAM at a dose of õ240 mg/day. South Carolina.Among 13 patients treated at or above this dose, there were 2 complete responses, 3 partial responses, 2 mixed responses, and 6 patients with progressive disease. The overall response rate for patients treated with 240 mg of TAM or higher was 38.5%. Dose-limiting toxicity, which occurred at a TAM dose of 280 mg/day, was Presented in part at the 31st Annual Meeting of primarily hematologic and gastrointestinal in nature. There was one toxic death the American Society of Clinical Oncology, Los Angeles, California, May 20-23, 1995.(due to septic neutropenia) at this dose. There were no episodes of thrombosis. CONCLUSIONS. A TAM dose of 240 mg/day is the recommended Phase II dose.Supported by Grant CA-51251 from the National Based on the 38.5% overall response rate at this dose, the authors have initiated Institutes of Health. treatment regimen, the overall response rate has been reported to those patients treated with the Dartmouth regimen with TAM com-

Tamoxifen induces p21WAF1 and p27KIP1 expression in estrogen receptor-negative lung cancer cells

“…Additionally, another work has indicated that more than 70% of NSCLC tumors showed reduced p27 KIP1 immunoreactivity and the expression of this CDKI was found to be a favorable prognostic factor for patient survival (Yatabe et al, 1998). It should be noted that the concentration of Tam used in this study can be attained in serum with high-dose Tam therapy (Trump et al, 1992;McClay et al, 1997). Collectively, these ®ndings indicate that Tam is a potent inducer of CDKI expression and an eective inhibitor of cell growth in NSCLC cells in vitro and this drug warrants further in vivo study.…”

A phase II study of two cycles of high-dose chemotherapy with autologous stem cell support in patients with metastatic breast cancer who meet eligibility criteria for a single cycle

“…The use of tamoxifen in this context was based upon previous reported studies from our institution describing synergism between high doses of tamoxifen and platinum chemotherapy. [17][18][19] Prophylactic heparin (5000 units s.c. three times daily day −5 to 0 ) was used to minimize the risk of thromboembolic complications. PBSC +/− BM were re-infused on day 0 as for HDC cycle I.…”

AMPK Activation and Metabolic Reprogramming by Tamoxifen through Estrogen Receptor–Independent Mechanisms Suggests New Uses for This Therapeutic Modality in Cancer Treatment

“…Furthermore, during the past two decades, over 25 clinical trials have been published reporting the effects of “high dose” tamoxifen (i.e. doses above those needed to inhibit ER activity) ranging from 80 to 720 mg/day (5) to treat non-breast cancers including glioma (6), melanoma (7) and others (8,9), as a single agent or in combination with chemotherapeutics. While of these Phase I and II trials showed variable clinical benefit, they clearly demonstrated the safety of high dose tamoxifen in diverse patient populations.…”