Sirolimus in treating patients with HIV-related Kaposi’s sarcoma

By | May 30, 2023

Sirolimus in treating patients with HIV-related Kaposi’s sarcoma. mTOR-targeting rapalogs in the treatment of various subtypes of sarcoma. Cancer 2011;. ? 2011 American Cancer Society. = .0001); Median OS, 88 wk with ridaforolimus vs 78.7 wk with placebo Open in a separate window Abbreviations: GIST, gastrointestinal stromal tumor; HR, hazard ratio; IV, intravenous; mTOR, mammalian target of rapamycin; OS, overall survival; PFS, progression-free survival; STS, soft tissue sarcoma; Mouse monoclonal to CD95(FITC) TSC, tuberous sclerosis complex. Temsirolimus A multicenter, phase 2 study evaluated weekly intravenous temsirolimus in chemotherapy-naive patients (N = 41) with advanced metastatic STS but failed to meet its clinical endpoints. Among 38 evaluable patients, 2 patients achieved a confirmed PR, including 1 patient with fibrosarcoma BAY-8002 and another patient with leiomyosarcoma (Table 1).86 The median time to progression was estimated at 2 months (95% confidence interval, 1.8-3.5 months). Most patients experienced AEs, with 43% of patients experiencing grade 3/4 events at least possibly related to treatment. Although these results indicate that treatment with temsirolimus alone does not seem to be a promising therapy for patients with advanced STS, it is important to note that the study endpoint was a confirmed tumor response to treatment, defined as a CR or PR on 2 consecutive evaluations at least 4 weeks apart.86 The exclusion of SD in the assessment of treatment outcome resulted in a lower treatment response BAY-8002 rate compared with other trials in sarcoma that evaluated other clinical endpoints, such as clinical benefit response, which incorporates SD. Another phase 2 trial examined intravenous temsirolimus in 52 pediatric patients with recurrent/refractory neuroblastoma, high-grade glioma, or rhabdomyosarcoma.92 Preliminary data from that trial indicated that 2 patients (1 neuroblastoma, 1 rhabdomyosarcoma) achieved a PR at 12 weeks and that 11 patients achieved SD that lasted for 12 weeks.92 Although the trial failed to meet its endpoint of tumor response (at least 2 patients in a subgroup needed to experience objective responses once 12 patients in that group had been enrolled), the responses observed and the clinical benefit attained by some patients suggest that further assessment may be warranted. Several ongoing phase 2 trials are evaluating the benefit of intravenous temsirolimus in patients with various subtypes of sarcoma. Temsirolimus is being BAY-8002 investigated as a single agent in patients with STS or GIST93 as well as patients with recurrent or persistent uterine cancer.94 Also, temsirolimus is being evaluated in combination studies with vinorelbine and cyclophosphamide in patients with recurrent or refractory rhabdomyosarcoma,95 and with selumetinib, a mitogen-activated protein kinase kinase (MEK) inhibitor, in patients with metastatic, recurrent, or locally advanced unresectable STS.93 Everolimus The oral agent everolimus has been studied as a combination therapy in a phase 2 trial in patients with BAY-8002 imatinib-resistant GIST. All patients received everolimus (2.5 mg daily) and imatinib (600 mg daily) (Table 1).87 Patients were enrolled in 2 strata: those who progressed after first-line treatment with BAY-8002 oral imatinib and those who progressed after imatinib and other therapies (most patients received oral sunitinib as second-line treatment). Of the 28 patients in the study who failed prior treatment with imatinib, 23 were evaluable, and 4 of those patients (17.4%) were progression-free at 4 months. In addition, 47 patients enrolled in the trial had failed treatment with first-line imatinib and second-line sunitinib; among the 35 patients who were evaluable, 13 (37.1%) were progression-free at 4 months. Most patients reported AEs: Sixty-seven percent experienced grade 3 or 4 4 AEs, and 48% experienced SAEs. These results suggest that patients with GIST may benefit from combined treatment in case.