Risk of renal failure in cancer patients with bone metastasis treated with renally adjusted zoledronic acid.

PURPOSE: The purpose of this study was to evaluate the incidence of acute renal failure (ARF) in patients with mild to moderate renal dysfunction, receiving renally adjusted zoledronic acid (ZA) and compare it to patients with normal baseline renal function, receiving standard-dose ZA. METHODS: This was a retrospective study of patients receiving ZA for the treatment of bone metastasis due to cancer. Patients were divided into two groups: (1) normal group with baseline creatinine clearance (CrCl) of greater than 60 mL/min and standard ZA dose; (2) impaired group with baseline CrCl of 30-60 mL/min and renally adjusted ZA dose. Primary endpoint of ARF was defined as an increase in serum creatinine (SCr) of 0.5 mg/dL or 1.0 mg/dL from a baseline SCr of <1.4 mg/dL or ≥ 1.4 mg/dL, respectively. RESULTS: In total, 1,472 evaluable doses of ZA were given to 220 patients. Of these, 184 patients were in the normal group and 36 patients in the impaired group. There were 38 patients (20.7%) who developed ARF in the normal group versus 7 patients (19.4%) in the impaired group. There was no difference in the mean time to the incidence of ARF at 6.1 months in both groups. Incidence of ARF based on CrCl (≥ 25% decline in CrCl) was similar between groups (39.1% vs. 41.7%; p = 0.78). CONCLUSION: The incidence of ARF is similar between patients in the normal group and impaired group when the ZA dose is renally adjusted.

Evaluation of chemotherapy-induced severe myelosuppression incidence in obese patients with capped dosing.

PURPOSE: Clinicians typically cap an obese patient's chemotherapy regimen as a result of concern for excessive toxicity, without adequate clinical evidence. The purpose of this study was to evaluate the incidence of grade 3 or 4 myelosuppression in obese patients versus nonobese patients with capped dosing on the basis of body surface area (BSA). METHODS: A retrospective chart review was conducted comparing obese patients (body mass index [BMI] ≥ 30 kg/m(2)) with capped dosing who received capped chemotherapy doses at a BSA of 2.2 m(2) with nonobese (BMI < 25 kg/m(2)) patients with lung, colorectal, or hormone-refractory prostate cancer. RESULTS: Forty-one obese patients with capped dosing and 244 nonobese patients were included. The obese patient group received on average significantly more cycles of chemotherapy (6 v 4 cycles) compared with the nonobese group. The overall incidence of any chemotherapy-related toxicity was 34% in the obese patient group, compared with 42% in the nonobese patient group (P = .356). The incidence of grade 3 or 4 myelosuppression was lower, but not statistically significant, in obese patients with capped dosing compared with the nonobese patient group (22% v 27%; P = .493). CONCLUSIONS: Overall, obese patients with capped dosing experienced a lower incidence of severe myelosuppression and tolerated more cycles of chemotherapy compared with nonobese patients. The better tolerability of chemotherapy in obese patients with capped dosing suggests that there is room to increase the dose in obese patients above the nationally recognized BSA cap of 2.0 m(2), especially in early-stage lung or colon cancers in which the intention of treatment is curative.

Comparison of the 5-fluorouracil-warfarin and capecitabine-warfarin drug interactions.

STUDY OBJECTIVE: To compare the differences between the 5-fluorouracil-warfarin and capecitabine-warfarin drug interactions in patients receiving therapeutic doses of warfarin. DESIGN: Retrospective medical record review. SETTING: Large academic Veterans Affairs health care system. PATIENTS: Twenty-four patients who received concomitant therapeutic doses of warfarin and at least one dose of a fluoropyrimidine--5-fluorouracil or capecitabine--between January 2004 and May 2008. MEASUREMENTS AND MAIN RESULTS: The primary outcome was mean change in international normalized ratio (INR) from baseline to end of 90-day study period. Only patients who were taking warfarin before starting either fluoropyrimidine-based chemotherapy were included in the primary analysis. Of the 24 eligible patients, 15 (9 receiving 5-fluorouracil, 6 receiving capecitabine) were taking warfarin before receiving either fluoropyrimidine. No significant differences were noted in the average weekly warfarin dose or baseline INR between the 5-fluorouracil and capecitabine groups. The mean change in INR for patients taking warfarin before fluoropyrimidine use was 4.62 in the 5-fluorouracil group compared with 5.11 in the capecitabine group (p=0.87). The capecitabine group had a similar proportion of patients achieving an INR above 9 while taking warfarin compared with the 5-fluorouracil group (17% vs 22%). In those patients who required a warfarin dosage reduction, the dose was reduced by 38% and 41% in the 5-fluorouracil and capecitabine groups, respectively. No significant differences in bleeding events were reported within 90 days of concurrent use of either fluoropyrimidine with warfarin. CONCLUSION: Our study suggests that in patients receiving concomitant warfarin and a fluoropyrimidine, no significant differences in INR elevation or bleeding events were noted with 5-fluorouracil compared with capecitabine.

Retrospective analysis of the consequences of acid suppressive therapy on ketoconazole efficacy in advanced castration-resistant prostate cancer.

BACKGROUND: The area under the curve of a single ketoconazole dose has been shown to decrease significantly when administered with acid suppressive therapy. No published studies have examined the clinical impact of concurrent ketoconazole and acid suppressive therapy in patients with castration-resistant prostate cancer (CRPC). OBJECTIVE: To evaluate the effect of acid suppressive therapy on prostate-specific antigen (PSA) response rate in CRPC patients receiving ketoconazole. METHODS: This retrospective study evaluated CRPC patients treated with ketoconazole 3 times daily between January 1, 1999, and September 30, 2009. Patients included in the analysis had failed androgen deprivation therapy, and were subsequently initiated on ketoconazole. Response (PSA decline ≥50% maintained ≥4 weeks) was evaluated in patients receiving ketoconazole with (group 1 [G1]) or without (group 2 [G2]) concurrent acid suppressive therapy. RESULTS: Thirty patients (G1: 11 patients; G2: 19 patients) were included in the analysis. Mean age in G1 and G2 was 71.8 and 69.6 years, respectively. Most patients had received prior therapy with an antiandrogen (90.9% G1; 100% G2) and fewer patients received antiandrogen withdrawal therapy (27.3% G1; 21.1% G2). Median baseline PSA was 109.4 (G1) and 86.9 ng/mL (G2) (p = 0.55). Median duration of ketoconazole was 7.2 months in G1 and 5.8 months in G2 (p = 0.09). Ketoconazole adherence was 82% (G1) and 100% (G2). Median duration of concurrent acid suppressive therapy was 3.8 months (range 2.0-20.4) in G1. PSA response (72.7% and 47.4%; p = 0.26) and time to PSA response (1.2 vs 0.9 mo; p = 0.53) were statistically similar between G1 and G2, respectively. Median progression free survival was higher in G1 (11.5 vs 6.9 months in G2; p = 0.047). CONCLUSIONS: Use of concurrent acid suppressive therapy and ketoconazole in CRPC patients did not decrease PSA response rate, and progression free survival was unexpectedly higher compared with the non-acid suppressive therapy group. Larger studies are needed to verify the clinical impact of acid suppressive therapy in combination with ketoconazole.