venlafaxine in preventing chronic oxaliplatin-induced neuropathy in patients receiving combination chemotherapy

Conditions: Peripheral Neuropathy

Summary: you are being asked to take part in this research study because you are going to be treated with oxaliplatin chemotherapy as part of your standard care. oxaliplatin commonly causes neuropathy (numbing, tingling and/or pain).the purpose of this study is to compare the effects, good and/or bad, of venlafaxine with a placebo (an inactive agent) on oxaliplatin-induced neuropathy (numbing, tingling and/or pain)

primary objectives: i. to explore whether venlafaxine can prevent or ameliorate chronic, cumulative neurotoxicity associated with oxaliplatin in cancer patients receiving oxaliplatin, fluorouracil, leucovorin calcium (folfox). secondary objectives: i. to explore whether venlafaxine can ameliorate acute neuropathy associated with oxaliplatin. tertiary objectives: i. to explore whether venlafaxine can increase the cumulative oxaliplatin doses that can be delivered without dose-limiting chronic neurotoxicity. ii. to explore whether venlafaxine causes adverse events in this setting. iii. to explore whether the neuropathy data provided by the rydel-seiffer graduated tuning fork is consistent with patient-reported outcome (pro) measures of chemotherapy-induced peripheral neuropathy (cipn) and whether this tool might cause different results in patients receiving venlafaxine versus placebo. outline: patients are randomized to 1 of 2 treatment arms. arm i: patients receive venlafaxine orally (po) twice daily (bid) beginning on day 1 of and continuing through completion of folfox. arm ii: patients receive placebo po bid beginning on day 1 of and continuing through completion of folfox. after completion of study treatment, patients are followed up at 1, 3, 6, 12, and 18 months.

Eligibility criteria:
inclusion criteria: * scheduled to receive folfox chemotherapy with individual oxaliplatin doses of 85 mg/m\^2 per cycle given in 2 week cycles (e.g. modified \[m\] folfox6 or folfox4) adequate complete blood count (cbc) and creatinine values (per attending physician) obtained =\ = 4 months strong inhibitors of cyp3a4: \> 5-fold increase in the plasma area under the curve (auc) values or more than 80 % decrease in clearance * indinavir (crixivan®) * nelfinavir (viracept®) * atazanavir (reyataz®) * ritonavir (norvir®) * clarithromycin (biaxin®, biaxin xl®) * itraconazole (sporanox®) * ketoconazole (nizoral®) * nefazodone (serzone®) * saquinavir (fortovase®, invirase®) * telithromycin (ketek®) inducers of cyp3a4 * efavirenz (sustiva®) * nevirapine (viramune®) * carbamazepine (carbatrol®, epitol®, equetro™, tegretol®, tegretol-xr®) * modafinil (provigil®) * phenobarbital (luminal®) * phenytoin (dilantin®, phenytek®) * pioglitazone (actos®) * rifabutin (mycobutin®) * rifampin (rifadin®) * st. john's wort exclusion criteria: any of the following: * pregnant women * nursing women history of an allergic reaction to, or intolerance of, venlafaxine treatment =\ 2-fold increase in the plasma auc values or 50-80% decrease in clearance * aprepitant (emend®) * erythromycin (erythrocin®, e.e.s. ®, ery-tab®, eryc®, eryped®, pce® * fluconazole (diflucan®) * grapefruit juice * verapamil (calan®, calan sr®, covera-hs®, isoptin sr®, verelan®, verelan pm®) * diltiazem (cardizem®, cardizem cd®, cardizem la®, cardizem sr®, cartia xt™, dilacor xr®, diltia xt®, taztia xt™, tiazac®) other medical conditions which, in the opinion of the treating physician/allied health professional, would make this protocol unreasonably hazardous for the patient prior neurotoxic chemotherapy concurrent radiotherapy current (within the last month) pre-existing peripheral neuropathy of any grade uncontrolled hypertension (defined as 3 consecutive readings over the past year of over 160 systolic, and over 100 diastolic)