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Table 3 Summary of clinical studies included in review of d-limonene and its derivatives on breast cancer

From: Effect of d-limonene and its derivatives on breast cancer in human trials: a scoping review and narrative synthesis

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.

  1. aIncluding breast cancer colorectal carcinoma, metastatic adenocarcinoma, esophagus, pancreas, bronchus, ovary, and soft tissue sarcoma
  2. bPartial response defined as ≥ 50% reduction in tumor size assessed by two measurements conducted ≥ 4 weeks apart
  3. cIncluding prostrate (n = 4), ovarian (n = 3), sarcoma, renal cell (n = 3), breast (n = 2), hepatocellular (n = 2), chronic myelogenous leukemia (n = 1), chronic lymphocytic leukemia (n = 1),adenocarcinoma (n = 1)
  4. dincluding: prostrate (n = 4), ovarian (n = 3), adenocarcinoma (n = 2), colorectal (n = 1), chronic myelogenous leukemia (n = 1), melanoma (n = 1), non-Hodgkin’s lymphoma (n-1), pancreas (n = 1), salivary gland (n = 1), and sarcoma (n = 1)
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BMC Cancer

ISSN: 1471-2407

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