Table 1. . Summary of tetrathiomolybate use and toxicity in early phase clinical trials.
| Study (year) | Study design: patient population | Subjects (n) | Drug dose | Concurrent therapies | Adverse events | Efficacy | Ref. |
|---|---|---|---|---|---|---|---|
| Brewer et al. (2000) | Phase I open-label dose escalation: solid metastatic cancers | 18 | 90, 105 and 250 mg/daily divided into six doses† | Trastuzumab (one patient) IFN and radiotherapy (two patients) |
Anemia, sulfur eructation | SD in 5/6 patients | [53] |
| Redman et al. (2003) | Phase II open-label: advanced kidney cancer | 15 | 180 mg/daily divided into four doses† | N/A | Fatigue, sulfur eructation, nausea, diarrhea, dizziness, self-limiting macular rash | 31% SD for at least 6 months during copper depletion (median: 34.5 weeks) | [49] |
| Henry et al. (2006) | Phase II open-label: hormone-refractory prostate cancer | 19 | 180 mg/daily divided into four doses† | N/A | Hematuria, neutropenia, lymphopenia, musculoskeletal pain, unstable angina | 14 PD, 1 BR | [52] |
| Pass et al. (2008) | Phase II open-label: post-operative malignant mesothelioma | 30 | 180 mg/daily divided into four doses† Maintenance: 80 mg/daily† |
N/A | Dizziness, fatigue, neutropenia, anemia, thrombocytopenia, fatigue, granulocytopenia, anemia | TTP 20 months in TM-treated vs 10 months non-TM-treated (p = 0.046) | [54] |
| Gartner et al. (2009) | Phase II open-label: metastatic colorectal cancer | 24 | 180 mg/daily divided into four doses† Maintenance: 80 mg/daily† |
Irinotecan 125 mg/m2, 5-FU 500 mg/m2, and leucovorin 20 mg/m2 | Neutropenia, anemia, diarrhea, nausea, vomiting | ORR 25%, median TTP 5.6 months | [51] |
| Jain et al. (2013) | Phase II open-label: histologically confirmed stage 3 or 4 breast cancer with NED | 40 | 180 mg/daily in four divided doses† Maintenance: 100 mg/daily† |
N/A | Anemia, leukopenia, neutropenia, sulfur eructation, fatigue | 10-month RFS was 85.0% | [50] |
| Nackos et al. (2015) | Phase II open-label: breast cancer with high risk for recurrence | 75 | 180 mg/daily divided into four doses† Maintenance: 100 mg/daily† |
N/A | Neutropenia, anemia | PFS 81% | [55] |
†Dose was titrated to optimal ceruloplasmin levels.
BR: Biochemical recurrence; ORR: Overall response rate; PD: Progressive disease; PFS: Progression-free survival; RFS: Relapse-free survival; SD: Stable disease; TTP: Time to progression.