Alternative temozolomide dosing regimens and novel combinations for the treatment of advanced metastatic melanoma
- PDF / 106,505 Bytes
- 11 Pages / 617.953 x 813.543 pts Page_size
- 34 Downloads / 156 Views
REVIEW
Alternative temozolomide dosing regimens and novel combinations for the treatment of advanced metastatic melanoma Wen-Jen Hwu • Ana E. Ayala • Ingrid M. Hernandez
Received: 10 July 2008 / Accepted: 2 August 2008 / Published online: 17 September 2008 ©Springer-Verlag 2008
Abstract Over the past 30 years, there has been no significant improvement in treatment outcomes for patients with advanced stage IV metastatic melanoma, and prognosis remains poor. Melanoma is known to be responsive to immunomodulatory agents, to be a highly vascular tumor, and to be fairly resistant to standard cytotoxic chemotherapy. Ongoing research is attempting to find novel combinations that may have therapeutic synergy. Alternative dosedense schedules of temozolomide appear promising and are being actively investigated, based on their potential to overcome chemoresistance to alkylating agents and the proven activity of temozolomide in the brain. Outcomes of studies investigating single-agent temozolomide suggest that it has activity similar to single-agent dacarbazine.
Other studies combining temozolomide with either interferon-alfa or thalidomide suggest that the addition of these immunomodulatory agents to temozolomide improves response rates and may improve overall survival. The best results have been achieved with the extended, daily, dosedense temozolomide regimen. Further research is needed to determine the optimal temozolomide regimen and best combination approach for the treatment of advanced metastatic melanoma.
Keywords Melanoma • Temozolomide • Interferon • Thalidomide • O6-methylguanine DNA methyltransferase
Introduction
W-J. Hwu (쾷) • A.E. Ayala • I.M. Hernandez The University of Texas, MD Anderson Cancer Center, Houston, TX, USA e-mail: [email protected]
Systemic therapy for stage IV melanoma consists of either single-agent chemotherapy, combination chemotherapy, immunotherapy with high-dose interleukin (IL)-2 in selected patients, or chemoimmunotherapy. Unfortunately, despite 30 years of intensive research, these approaches have not resulted in any marked improvement in survival since the US Food and Drug Administration approved dacarbazine (DTIC) in 1975. Research efforts over the past ten to 15 years have focused on chemoimmunotherapy regimens, vaccines, and novel targeted agents, with only limited success. Perhaps the biggest disappointment was the failure of chemoimmunotherapy, which had been heralded as a significant advance based on high objective response rates of approximately 60% [1, 2]. However, randomized controlled trials showed that these regimens did not improve survival compared with combination chemotherapy [3]. Median overall survival for this patient population
13
184
has remained relatively unchanged for the last 30 years. In general, melanoma cells are highly resistant to cytotoxic chemotherapy [4]. Although biological agents, including IL-2 and interferon-alfa (IFN-α) have demonstrated modest activity and IL-2 produces durable complete responses in approximately 5% of treated patient
Data Loading...
