Abstract
Purpose
Temozolomide and fotemustine are both active drugs for treating metastatic melanoma. The present study was designed to assess the efficacy and safety of combination therapy with temozolomide + fotemustine in patients with metastatic melanoma.
Methods
Forty patients (median age 50.5 and 22 males) with pathologically confirmed, unresectable, AJCO stage IV melanoma were enrolled into the study. The primary endpoints were tumor response and safety. Patients received oral temozolomide 125 mg/m2 on days 1–7 and intravenous fotemustine 80 mg/m2 on day 3 every 3 weeks.
Results
Fourteen (35%) patients achieved an objective response, including 3 (7.5%) complete and 11 (27.5%) partial responses. Median overall survival time was 6.7 months and 6-month survival rate was 57.4%. Myelosupression, particularly thrombocytopenia, was the primary toxicity.
Conclusion
The regimen, temozolomide combined with fotemustine, is an active and moderately safe first-line chemotherapy regimen with acceptable and easily manageable toxicities in patients with metastatic melanoma.
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References
Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, et al (2001) Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19:3635–3648
Li Y, McClay EF (2002) Systemic chemotherapy for the treatment of metastatic melanoma. Semin Oncol 29:413–426
Balch CM, Atkins MB, Sober AJ (2005) Cutaneous melanoma. In: Devita VT Jr, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology. Lippincott Williams and Wilkins, Philadelphia, pp 1754–1809
Chapman PB, Einhorn LH, Meyers ML, Saxman S, Destro AN, Panageas KS, et al (1999) Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol 17:2745–2751
Middleton MR, Lorigan P, Owen J, Ashcoft L, Lee SM, Harper P, et al (2000) A randomized phase III study comparing dacarbazine, BCNU, cisplatin and tamoxifen with dacarbazine and interferon in advanced melanoma. Br J Cancer 82:1158–1162
Newlands ES, Stevens HF, Wedge SR, Wheelhouse RT, Brock C (1997) Temozolomide: a review of its discovery, chemical properties, pre-clinical development and clinical trials. Cancer Treat Rev 23:35–61
Newlands ES, Blackledge GR, Slack JA, Rustin GJ, Smith DB, Stuart NS, et al (1992) Phase I trial of temozolomide. Br J Cancer 65:287–291
Bleehan NM, Newlands ES, Lee SM, Thatcher N, Selby P, Calvert AH, et al (1995) Cancer Research Campaign phase II trial of temozolomide in metastatic melanoma. J Clin Oncol 13:910–913
Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, et al (2000) Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 18:158–166
Bafaloukos D, Gogas H, Georgoulias V, Briassoulis E, Fountzilas G, Samantas E, et al (2002) Temozolomide in combination with docetaxel in patients with advanced melanoma: a phase II study of the Hellenic Cooperative Oncology Group. J Clin Oncol 20:420–425
Hwu WJ, Krown SE, Menell JH, Panageas KS, Merrell J, Lamb LA, et al (2003) Phase II study of temozolomide plus thalidomide for the treatment of metastatic melanoma. J Clin Oncol 21:3351–3356
Danson S, Lorigan P, Arance A, Clamp A, Ranson M, Hodgetts J, et al (2003) Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma. J Clin Oncol 21:2551–2557
Tas F, Argon A, Camlica H, Topuz E (2005) Temozolomide in combination with cisplatin in patients with metastatic melanoma: a phase II trial. Melanoma Res 15(6):543–548
Spiro TP, Liu L, Majka S, Haaga J, Willson JLKV, Gerson SL (2001) Temozolomide: the effect of once-and twice-a-day dosing on tumor tissue levels of the DNA repair protein O6-Alkylguanine-DNA-Alkyltransferase. Clin Cancer Res 7:2309–2317
Tolcher AW, Gerson SL, Denis L, Geyer C, Hammond LA, Patnaik A, et al (2003) Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. Br J Cancer 88:1004–1011
Marzolini C, Decosterd L, Shen F, Gander M, Leyvraz S, Bauer J, et al (1998) Pharmacokinetics of temozolomide in association with fotemustine in malignant melanoma and malignant glioma patients: comparison of oral, intravenous, and hepatic intra-arterial administration. Cancer Chemother Pharmacol 42:433–440
Gander M, Leyvraz S, Decosterd L, Bonfanti M, Marzolini C, Shen F, et al (1999) Sequential administration of temozolomide and fotemustine: depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours. Ann Oncol 10:831–838
Aamdal S, Gerard B, Bohman T, D’Incalci M (1992) Sequential administration of dacarbazine and fotemustine in patients with disseminated malignant melanoma—an effective combination with unexpected toxicity. Eur J Cancer 28:447–450
Lee SM, Margison GP, Woodcock AA, Thatcher N (1993) Sequential administration of varying doses of dacarbazine and fotemustine in advanced malignat melanoma. Br J Cancer 67:1356–1360
Plowman J, Waud WR, Koutsoukos AD, Rubinstein LV, Moore TD, Grever MR (1994) Preclinical antitumor activity of temozolomide in mice: efficacy against human brain tumour xenographs and synergism with 1,3-bis(2-chloroethyl)-1-nitro-sourea. Cancer Res 54:3793–3799
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Tas, F., Camlica, H. & Topuz, E. Temozolomide in combination with fotemustine in patients with metastatic melanoma. Cancer Chemother Pharmacol 62, 293–298 (2008). https://doi.org/10.1007/s00280-007-0606-5
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DOI: https://doi.org/10.1007/s00280-007-0606-5