Human clinical trials reporting statin use in cancer therapy
| Study | Statin | n | Tumor Type | Therapeutic Protocol | Results | Side Effects |
|---|---|---|---|---|---|---|
| Thibault et al. (1996) | Phase I: | 88 | 38 Prostate | p.o. for 7 consecutive days in monthly cycles, increasing doses in the next cycle when well tolerated in the first | Minor response (45% reduction in tumor size maintained for 8 months) in one anaplastic astrocytoma | Incidence and severity of toxicity (mainly myopathy, nausea, diarrhea, fatigue, abdominal pain) increasing for dose level higher than 25 mg/kg |
| Myalgias partially controlled by ubiquinone administration | ||||||
| Lovastatin (2–45 mg/kg/day) | ||||||
| 24 Primary central nervous system | ||||||
| 7 Breast | ||||||
| 4 Colorectal | ||||||
| 4 Ovary | ||||||
| 3 Sarcoma | ||||||
| 2 Lung | ||||||
| 6 Others | ||||||
| Vitols et al. (1997) | Open nonrandomized pilot study: simvastatin (40 mg) | 10 | B-cell CLL previously untreated | p.o. 40 mg daily by a single oral dose for 12 weeks | No significant change in the clinical disease status during treatment; 40% of patients developed progressive disease during the subsequent year and 60% within 2 years after stopping simvastatin | No adverse reactions experienced during the treatment |
| Larner et al. (1998) | Phase I: lovastatin | 18 | Anaplastic glioma or glioblastoma multiforme | Lovastatin 30 mg/kg/day for 7 days at 4-week interval; recurrent disease after radiotherapy (n = 9) received lovastatin alone; newly diagnosed patients (n = 9) received radiotherapy plus lovastatin | One partial response; one minor response; one stable disease for a period longer than 400 days | Mild toxicity; mild pain in 2 patients |
| Kawata et al. (2001) | Randomized controlled trial: pravastatin (40 mg) | 83 | HCC pretreated with TAE, infusion of 30 mg doxorubicin) followed by oral 5-FU (200 mg daily) for 2 months | Pravastatin group (n = 41): p.o 20 mg/day for 2 weeks, followed by 40 mg/day (for 16.5 ± 9.8 months); control group (n = 42), not treated with any anticancer drugs. | No significant differences in Karnofsky performance status between treated and control group; slight improvement or stable status in the liver functions in treated group compared with control; in pravastatin-treated group, median survival higher than in control group (18 vs. 9 months) | No adverse reactions experienced during the treatment |
| Kim et al. (2001) | Phase II: lovastatin (35 mg/kg/day) | 16 | Locally advanced and metastatic adenocarcinoma of the stomach, previously treated with systemic chemotherapy | p.o. 35 mg/kg/day in four divided doses for 7 consecutive days in monthly cycles (median, two cycles) ubiquinone (p.o. 240 mg daily) coadministered with lovastatin | No significant responses | Anorexia in the 64% of patients; myalgia in two patients (12.5%) |
| Minden et al. (2001) | Case report lovastatin | 1 | Relapsed AML | 40 mg/day | Partial control of the leukemic blast cells | Not reported |
| Lersch et al. (2004) | Randomized controlled trial: pravastatin (40–80 mg) | 58 | HCC previously treated with 3 × 200 μg/day octreotide for 2 months | Octreotide group (n = 30): 20 mg octreotide LAR every 4 weeks; pravastatin group (n = 20), 40–80 mg pravastatin; gemcitabine group (n = 8), 80–90 mg/m2 over 24 h weekly in cycles of 4 weeks | No significant differences in tumor responses; pravastatin failed to prolong median survival | Not reported |
| Katz et al. (2005) | Retrospective multivariate analysis: all statins | 349 | Clinically resectable nonmetastatic rectal cancers; among these 33 statin users | Presurgery neoadjuvant chemoradiation (median dose, 50.4 Gy) and concurrent chemotherapy with 5-FU | No differences in clinical stages at time of diagnosis; in statin users, improved pathologic complete response rate after neoadjuvant chemoradiation | |
| Knox et al. (2005) | Phase I: Lovastatin (5–10 mg/kg/day) | 26 | 14 HNSCC and 16 CC, advanced or recurrent | Lovastatin (5–10 mg/kg/day) for 2 weeks every 21 days | No significant responses; slight effect in disease stabilization | Muscle toxicity at 10 mg/kg/day for 14 days |
| Graf et al. (2008) | Cohort study: pravastatin | 183 | HCC patients selected for palliative treatment by TACE: 52 received TACE combined with pravastatin; 131 received chemoembolization alone | Pravastatin (20–40 mg/day) | In HCC treated by TACE and pravastatin, median survival was significantly longer than that in HCC treated by TACE alone (20.9 vs. 12.0 months) | Not reported |
| Kornblau et al. (2007) | Phase I: Pravastatin (40–1680 mg/day) | 37 | 15 Newly diagnosed patients with AML; 22 salvage patients with AML | Pravastatin (40–1680 mg/day) administered p.o. once daily for 8 days; idarubicin (12 mg/m2/day), intravenously, days 4–6; and cytarabine (1.5 g/m2/day) by continuous infusion, days 4–7, coadministered with pravastatin | Among 15 newly diagnosed patients 11 experienced complete remission; in 9 of 22 salvage patients, a complete remission was obtained | No toxicity occurred at a frequency higher than that expected with the standard idarubicin-cytarabine protocols; no significant increase in the frequency and severity of toxicity associated with pravastatin dose escalation. |
| Lee et al. (2009) | Phase II: Simvastatin | 49 | Metastatic adenocarcinoma of the colon or rectum | Simvastatin (40 mg, p.o. once daily during the period of chemotherapy) coadministered with FOLFIRI (irinotecan 180 mg/m2/90-min infusion; leucovorin 200 mg/m2, 2-h infusion; 5-FU 400 mg/m2 bolus injection followed by 2400 mg/m2 as a 46-h continuous infusion), repeated every 2 weeks | Response rate (46,9%) and median survival time (21.9 months) similar to that obtained with FOLFIRI alone; modestly prolonged TTP (9,9 months) compared with FOLFIRI alone | No toxicity higher than that induced by FOLFIRI alone; no patients experienced myotoxicity or increase in serum creatine phosphokinase |
CLL, chronic lymphocytic leukemia; TAE, transcatheter arterial embolization; CC, cervix carcinoma; HNSCC, head and neck SCC.