Cutaneous T Cell Lymphoma: Responses in Phase 1 Trial of Combination Therapy with Liposomal Doxorubicin, Bortezomib, and Gemcitabine.

BACKGROUND: There is preclinical data suggesting pro-apoptotic synergy between the proteosome inhibitor bortezomib, doxorubucin and gemcitabine. Therefore, we are currently conducting a Phase I dose finding trial of this combination. As a part of this trial, high response rates with excellent tolerance were noted in advanced cutaneous T- cell lymphoma, and are presented here.

METHODS: A 3+ 3 design was used. There were two cohorts of patients: < 65 and ≥65 years of age. The older cohort was dose escalated after the younger cohort demonstrated safety at a dose level. Initial dose escalations were in bortezomib alone, followed by gemcitabine, and then by liposomal doxorubicin.

RESULTS: There were 33 patients who were treated on this trial to date. We are reporting the results of 7 patients with cutaneous T cell lymphoma. These patients had been heavily pretreated with a median of 6 prior therapies (range 1–12). All six of six evaluable patients (100%) achieved a partial remission (PR). Some of these responses are ongoing and the patients are still improving. The most common toxicities were grade 2 thrombocytopenia (50% of patients), grade 1–2 fatigue (44% patients), grade1–2 mucositis (14% patients), and myelosuppression (12% patients). Four patients needed hospitalization early in the course for sepsis. All of these patients had advanced disease with ulcerating skin lesions. Dose limiting toxicity has not been seen.

CONCLUSIONS: The above combination is safe up to the doses tested so far- (dose level 5 = doxil 24mg/m2 on day1, gemcitabine 800 mg/m2 on days 1 and 8 and bortezomib 1.0 mg/m2 on days 1,4,8,11) and has activity in heavily pretreated, advanced cutaneous T-Cell lymphoma.