Phase II Study of Temozolomide and Thalidomide in Patients with Unresectable or Metastatic Leiomyosarcoma

Michelle S Boyar, Mary Hesdorffer, Mary Louise Keohan, Zhezhen Jin, Robert N Taub, Michelle S Boyar, Mary Hesdorffer, Mary Louise Keohan, Zhezhen Jin, Robert N Taub

Abstract

We assessed the efficacy of combined temozolomide and thalidomide in patients with unresectable or metastatic leiomyosarcoma in a phase II single-institution trial. Twenty-four patients were enrolled. Temozolomide (150 mg/m(2)/day for 7 days every other week) was administered with concomitant thalidomide (200 mg/day), and continued until unacceptable toxicity or disease progression. There were no complete responses and two (10%) partial responses. Five patients (24%) had stable disease for at least six months. Fourteen patients (67%) progressed after a median of two-month treatment. The median overall survival (twenty-two assessable patients) was 9.5 months [95% CI 7-28 months]. There were no treatment-related deaths or CTC grade 4 toxicities. Thirteen patients were dose-reduced or discontinued thalidomide due to toxicity. In conclusion, this combination of temozolomide and thalidomide provided disease stabilization in a subset of patients with advanced leiomyosarcoma. We hypothesize that temozolomide is the active agent in this regimen, and should be further studied.

Figures

Figure 1
Figure 1
Time for disease progression.
Figure 2
Figure 2
Overall survival.

References

    1. Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA: A Cancer Journal for Clinicians. 2005;55(1):10–30.
    1. Edmonson JH, Ryan LM, Blum RH, et al. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. Journal of Clinical Oncology. 1993;11(7):1269–1275.
    1. Antman KH, Ryan L, Elias A, Sherman D, Grier HE. Response to ifosfamide and mesna: 124 previously treated patients with metastatic or unresectable sarcoma. Journal of Clinical Oncology. 1989;7(1):126–131.
    1. Gottlieb JA, Benjamin RS, Baker LH, et al. Role of DTIC (NSC-45388) in the chemotherapy of sarcomas. Cancer Treatment Reports. 1976;60(2):199–203.
    1. Borden EC, Amato DA, Rosenbaum C, et al. Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas. Journal of Clinical Oncology. 1987;5(6):840–850.
    1. Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. The New England Journal of Medicine. 2002;347(7):472–480.
    1. Brennan MF, Casper ES, Harrison LB. Soft tissue sarcoma. In: DeVita VT Jr., Hellman S, Rosenberg SA, editors. Cancer Principles and Practice of Oncology. 5th edition. Philadelphia, Pa, USA: Lippincott-Raven; 1997. pp. 1738–1788.
    1. Tsang LLH, Quarterman CP, Gescher A, Slack JA. Comparison of the cytotoxicity in vitro of temozolomide and dacarbazine, prodrugs of 3-methyl-(triazen-1-yl)imidazole-4-carboxamide. Cancer Chemotherapy and Pharmacology. 1991;27(5):342–346.
    1. Stevens MFG, Newlands ES. From triazines and triazenes to temozolomide. European Journal of Cancer Part A. 1993;29(7):1045–1047.
    1. Bower M, Newlands ES, Bleehen NM, et al. Multicentre CRC phase II trial of temozolomide in recurrent or progressive high-grade glioma. Cancer Chemotherapy and Pharmacology. 1997;40(6):484–488.
    1. Middleton MR, Grob JJ, Aaronson N, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. Journal of Clinical Oncology. 2000;18(1):158–166.
    1. Talbot SM, Keohan ML, Hesdorffer M, et al. A phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma. Cancer. 2003;98(9):1942–1946.
    1. Trent JC, Beach J, Burgess MA, et al. A two-arm phase II study of temozolomide in patients with advanced gastrointestinal stromal tumors and other soft tissue sarcomas. Cancer. 2003;98(12):2693–2699.
    1. Woll PJ, Judson I, Lee SM, et al. Temozolomide in adult patients with advanced soft tissue sarcoma: a phase II study of the EORTC Soft Tissue and Bone Sarcoma Group. European Journal of Cancer. 1999;35(3):410–412.
    1. Kumar S, Rajkumar SV. Thalidomide and lenalidomide in the treatment of multiple myeloma. European Journal of Cancer. 2006;42(11):1612–1622.
    1. Hwu W-J, Krown SE, Menell JH, et al. Phase II study of temozolomide plus thalidomide for the treatment of metastatic melanoma. Journal of Clinical Oncology. 2003;21(17):3351–3356.
    1. Kulke MH, Stuart K, Enzinger PC, et al. Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. Journal of Clinical Oncology. 2006;24(3):401–406.
    1. Garcia del Muro X, Lopez-Pousa A, Martin J, et al. A phase II trial of temozolomide as a 6-week, continuous, oral schedule in patients with advanced soft tissue sarcoma: a study by the spanish group for research on sarcomas. Cancer. 2005;104(8):1706–1712.
    1. Anderson S, Aghajanian C. Temozolomide in uterine leiomyosarcomas. Gynecologic Oncology. 2005;98(1):99–103.
    1. Hegi ME, Diserens A-C, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. The New England Journal of Medicine. 2005;352(10):997–1003.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner