Author(s) | Trial Phase | Compound | Cancer type | Dose | Toxicity | Maximum tolerated dose | Effect on breast cancer |
---|---|---|---|---|---|---|---|
d-limonene | |||||||
 Vigushin et al. 1998 [22] | Phase 1: Human subjects (n = 32) | Orally administered d-limonene | Phase 1: refractory solid tumorsa | 0.5 to 12 g/m2 per day in 21-day cycles | Gastrointestinal toxicities leading to nausea, vomiting and diarrhea were dose limiting | 8 g/m2 per day | Phase 1: Partial responseb observed in one breast cancer patient. Effect was sustained for 11 months. |
Phase 2: Human subjects (n = 10) | Phase 2: locally advanced breast cancer | 8 g/m2 per day for 15 cycles | Not indicated | Phase 2: no response | |||
 Miller et al. 2013 [26] | Phase 2: Human subjects (n = 43) | Orally administered d-limonene | Newly diagnosed, operable cancers breast cancer | 2 g d-limonene for 2–6 weeks | Well tolerated | Not indicated | D-limonene concentrated in breast tissue (mean 41.3 μg/g tissue); Small but statistically significant increase in insulin-like growth factor levels; Reduction in tumor cyclin D1 expression |
Perillyl alcohol | |||||||
 Ripple et al. 1998 [23] | Phase 1: Human subjects (n = 18) | Orally administered perillyl Alcohol | Advanced malignanciesc | Dose escalation: 800, 1200 and 1600 mg/m2/dose administered 3 time a day | Dose- related gastrointestinal toxicities leading to nausea and vomiting; 2 participants experienced severe drug related myelosuppression | Not indicated | No objective tumor response observed in any patients |
 Ripple et al. 2000 [24] | Phase 1: Human subjects (n = 16) | Orally administered perillyl Alcohol | Advanced refractory malignanciesd | Dose escalation: 800, 1600 and 2400 mg/m2/dose administered 4 time a day | Gastrointestinal toxicities, including nausea, vomiting, satiety, and eructation, that were dose limiting | 1200 mg/m2/dose | No anticancer activity observed in breast cancer patient. Tumor regression observed in one patient with metastatic colorectal cancer |
 Bailey et al. 2008 [25] | Phase 2: Women (N = 14) | Orally administered perillyl Alcohol | Advanced treatment-refractory breast cancer | Dose escalation: 1200–1500 mg/m2/dose administered 4 time a day | Poor toleration due to gastrointestinal and fatigue- related toxicities | Not indicated | No partial or complete regression observed in any participant. |