Table 1.

Adverse events observed in each protocol listed alphabetically by dose level

Sirolimus aloneSirolimus plus ketoconazoleSirolimus plus grapefruit juice
Adverse event10 mg20 mg30 mg60 mg30 mg (4 h)30 mg (24 h)45 mg (24 h)1 mg2 mg3 mg4 mg5 mg6 mg8 mg16 mg15 mg20 mg25 mg30 mg35 mgTotal (n = 138)
Altered taste111115
Anemia3534 (1)3325 (1)314 (2)4 (1)11446 (5)
Anorexia111 (1)315121132231432 (1)
Decreased platelets111111122313422
Diarrhea1526 (1)423 (1)211241 (1)235431658 (3)
Mucocutaneous dryness111126
Dyspnea11211 (1)6 (1)
Edema131 (1)5 (1)
Elevated creatinine11
Elevated transaminases142111 (1)1 (1)13421123 (2)
Epistaxis11
Fatigue241514141213 (1)6 (1)2225 (1)46 (3)
Fever2114
Hand and foot syndrome112
Hyperlipidemia243 (1)6 (1)313342269 (1)112759 (3)
Hyperglycemia664114 (1)5424324 (2)10 (1)3 (1)4 (1)27 (1)72 (7)
Hypocalcemia22
Hypertension112
Hypoglycemia1 (1)1 (1)
Hypoxia22
Infection11 (1)1 (1)11 (1)1 (1)11311114 (4)
Leukopenia212212112317
Lymphopenia3 (2)4 (1)3 (1)3422 (1)3 (1)3 (1)5 (2)23 (1)7 (1)2 (1)42 (1)4 (1)56 (14)
Mood alteration112
Mucositis21112112121217
Myalgia213
Nail changes1 (1)1 (1)
Nausea324 (1)621221214226 (1)22448 (2)
Neutropenia1111217
Paresthesia112
Pleural effusion11
Pneumonia2 (2)12 (2)5 (4)
Pruritis121116
Rash1111111212214
Vomiting22524311 (1)221311333 (1)
Weight loss421111111215

NOTE: Numbers in parentheses represent grade 3 or 4 toxicity.