Table 1.
Completed Oncology Trials of Temsirolimus (IV administration)
| Study | Patient Population (N) |
Treatment | Efficacy | Safety |
|---|---|---|---|---|
| Phase I dose escalation46 | Advanced cancer (24) | Temsirolimus 7.5–220 mg/m2 weekly | PR: n = 2 | Treatment-related acne-like, maculopapular rashes and mucositis or stomatitis |
| Phase I34 | Advanced cancer (63) | Temsirolimus 0.75–24 mg/m2 | PR, n = 4 (3 unconfirmed) SD, n = 2 |
Treatment-related asthenia, mucositis, nausea and cutaneous toxicity |
| Phase II33 | Metastatic renal cell carcinoma (111) | Temsirolimus 25, 75 or 250 mg weekly | ORR: 7% CR: n = 1 PR: n = 7 Minor response: 26% TTP: 5.8 months OS: 15.0 months |
Grade 3/4 hyperglycemia (17%), hypophosphatemia (13%), anemia (9%), hypertriglyceridemia (6%) |
| Phase I/II48 | Metastatic renal cell carcinoma (39) | Temsirolimus 15 mg weekly plus interferon-α | PR: n = 3 SD: n = 14 PFS: 7.6 months |
Grade 3/4 leukopenia, hypophosphatemia, asthenia, anemia, hypertriglyceridemia |
| Phase III7 | Metastatic renal cell carcinoma (626) | Temsirolimus 25 mg weekly Interferon-α Temsirolimus 15 mg weekly + interferon-α |
ORR: 8.6%, 4.8%, 8.1% OS: 10.9, 7.3, 8.4 months PFS: 3.8, 1.9, 3.7 months (local) 5.5, 3.1, 4.7 months (independent) |
Temsirolimus: grade 3/4 anemia (20%), asthenia (11%), hyperglycemia (11%), dyspnea (9%), infection (5%) |
| Phase II35 | Locally advanced or metastatic breast cancer (109) | Temsirolimus 75 or 250 mg weekly | ORR: 9% PR: n = 10 TTP: 12.0 weeks |
Grade 3/4 mucositis (9%), leukopenia (7%), hyperglycemia (7%), somnolence (6%), thrombocytopenia (5%) and depression (5%) |
| Phase III51 | Postmenopausal locally advanced BC or mBC | Temsirolimus 30 mg daily for 5 days every 2 weeks + letrozole 2.5 mg daily (n = 556) Placebo + letrozole 2.5 mg daily (n = 556) |
Temsirolimus + letrozole, PFS: 8.8 months ORR: 27% CR: n = 11 PR: n = 139 SD: n = 100 Placebo + letrozole, PFS: 8.9 months ORR: 27% CR: n = 11 PR: n = 139 SD: n = 106 |
Temsirolimus + letrozole, grade 3/4 hyperglycemia (4%), dyspnea (3%), neutropenia (3%), asthenia (3%) Placebo + letrozole, grade 3/4 dyspnea (3%), asthenia (2%), hyperglycemia (1%), neutropenia (1%) |
| Phase II47 | Mantle cell lymphoma (35) | Temsirolimus 250 mg weekly | ORR: 38% CR: n = 1 PR: n = 12 TTP: 6.5 months DOR: 6.9 months |
Grade 3/4 thrombocytopenia (66%), neutropenia (29%), anemia (26%) |
| Phase II50 | Mantle cell lymphoma (29) | Temsirolimus 25 mg weekly | ORR: 41% CR: n = 1 PR: n = 10 TTP: 6 months DOR: 6 months |
Grade 3/4 thrombocytopenia (39%), fatigue (25%), neutropenia (18%), anemia (15%) |
| Phase III36 | Mantle cell lymphoma (162) | Temsirolimus 175 mg weekly for 3 weeks then: 75 mg, 25 mg or investigators choice | ORR, 22%, 6%, 2% PFS: 4.8, 3.4, 1.9 months OS: 12.8, 10.0, 9.7 months CR: n = 1, 0, 1 PR: n = 11, 3, 0 |
Grade 3/4 thrombocytopenia (59%, 52%, 36%), anemia (20%, 11%, 17%), neutropenia (15%, 22%, 26%), asthenia (13%, 19%, 8%) |
| Phase II49 | Recurrent or metastatic endometrial carcinoma, chemotherapy-naive (33, 29 evaluable for tumor response) or chemotherapy-treated (27, 25 evaluable for tumor response) | Temsirolimus 25 mg weekly | Chemotherapy-naïve PR: n = 7 SD: n = 20 Chemotherapy-treated: PR: n = 2 SD: n = 12 |
Chemotherapy-naive: grade 3 fatigue (12%), diarrhea (6%), pneumonitis (6%) Chemotherapy-treated: grade 3 fatigue (11%), diarrhea (11%), pneumonitis (11%), dyspnea (7%), grade 3/4 hypokalemia (11%) |
ORR, overall response rate; OS, overall survival; TTP, time-to-progression; DOR, duration of response; PR, partial response; CR, complete response.