Reduced-dose rasburicase in the treatment of adults with hyperuricemia associated with malignancy.

Tumor lysis syndrome is a life-threatening complication of chemotherapy for patients with leukemia and large tumors with a high proliferative index, such as Burkitt's lymphoma. The syndrome is characterized by hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia. The standard of care for hyperuricemia consists of hydration with or without alkalinization and administration of allopurinol. When treated in this manner, patients often experience persistent hyperuricemia that lasts several days after the start of antineoplastic therapy; sometimes they develop uric acid nephropathy as a consequence. Rasburicase, a recombinant urate oxidase enzyme, quickly removes large amounts of uric acid from plasma. The drug is approved by the United States Food and Drug Administration for management of elevated plasma uric acid levels in pediatric patients with leukemia, lymphoma, or solid tumor malignancies who are receiving chemotherapy. We undertook a retrospective review of adult patients treated with a single dose of rasburicase 6 mg for hyperuricemia associated with malignancy. Ten patients received one 6-mg dose of rasburicase, and one patient received two 6-mg doses as an adjuvant therapy to normalize uric acid levels. In most of the patients, a single 6-mg dose of rasburicase was effective in correcting uric acid levels in the typical time between diagnosis and start of antineoplastic therapy.

Intrathecal topotecan in adult patients with neoplastic meningitis.

PURPOSE: The efficacy and safety of intrathecal topotecan were assessed in patients with neoplastic meningitis (NM) by retrospective chart review. SUMMARY: Fourteen patients (median age, 57 years) with NM were treated with the standard of care (i.e., regional or systemic chemotherapy or irradiation or both) plus intrathecal topotecan between January 2004 and September 2005. Three patients developed NM in the setting of systemic cancer; 11 patients had primary central nervous system (CNS) malignancies. All patients received 0.4 mg of topotecan intrathecally two times per week. The efficacy of intrathecal topotecan was assessed on the basis of the number of doses to cerebrospinal fluid (CSF) cytologic clearing--defined as the disappearance of malignant cells from a previously positive CSF cytology. Safety was evaluated by chart documentation of adverse events that might have been associated with topotecan given intrathecally. Of the 11 patients with primary CNS tumors, 6 patients achieved CSF clearing after the first dose of intrathecal topotecan, 2 patients after the second dose, and 1 patient after the fifth dose. For the 3 patients with secondary CSF tumors, 1 patient achieved CSF clearing after the third dose and 2 patients did not reach the primary endpoint. Overall, 6 of the 14 patients achieved CSF clearing after the first dose of intrathecal topotecan; in 10 of the 14 patients, CSF clearing of malignant cells was observed at some point during treatment. Toxicity was modest. The most common adverse effect reported was fatigue. CONCLUSION: Intrathecal topotecan appeared to be effective and safe in adult patients with NM.

Safety and cost-effectiveness of paclitaxel administered as a 1-hour infusion versus a 3-hour infusion for various malignancies.

This study challenges the current practice of administering paclitaxel for a variety of malignancies over 3 hours and documents the safety and cost-effectiveness of 1-hour administration in the outpatient setting. The authors investigated opportunities to save nursing time and costs in a cancer clinic without compromising patient safety. These savings are referred to as "opportunity-cost savings" that enable the clinic to schedule more patients during the time normally required to administer a 3-hour paclitaxel dose. Over a 2-year period, the authors were able to document significant time savings with no increase in adverse drug reactions.

Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy in the treatment of peritoneal carcinomatosis.

PURPOSE: Cytoreductive surgery (CS) and intraperitoneal hyperthermic chemotherapy (IPHC) in the treatment of peritoneal carcinomatosis (PC) in 15 patients are described. SUMMARY: Fifteen patients with PC who were treated with CS and IPHC were retrospectively identified between January 2002 and December 2006. All patients underwent cytoreduction immediately followed by IPHC with mitomycin or cisplatin. The time between undergoing CS and IPHC and the date of the last follow-up appointment or the date of death was used to calculate survival data for each patient. Nine patients had complete cytoreduction, and all but one patient had evidence of invasive disease at the time of surgery. Eleven patients required concomitant bowel resection at the time of debulking. Thirteen patients required blood transfusions during the perioperative period. Nine patients were discharged home, and four were discharged to a rehabilitation facility. Two patients died during the perioperative hospital admission, both of whom had a preoperative Eastern Cooperative Oncology Group (ECOG) performance status score of 2. The median survival time was 8.4 months, similar to the findings of previously published studies. Further studies are needed to see if tumor type, ECOG performance status score, degree of cytoreduction, and the chemotherapy agent used in IPHC can be correlated to quality of life and survival in patients with heterogeneous primary sources of intraabdominal malignancies. CONCLUSION: Combination treatment with CS followed by IPHC in 15 patients with heterogeneous primary sources of intraabdominal malignancies resulted in a median survival time of 8.4 months.

Intraurethral fluorouracil and lidocaine for intraurethral condyloma acuminata.

PURPOSE: A new and convenient means of administering fluorouracil and lidocaine for the treatment of intraurethral condyloma acuminata is discussed. SUMMARY: Condyloma acuminata are warts of the genital and perianal region caused by various types of human papillomavirus (HPV). Intraurethral condylomas are associated with complications such as urinary burning, frequency, urgency, urethral bleeding, obstruction, fistula formation, and dyspareunia. A 55-year-old white man had a chief complaint of profuse, but painless, hematuria when he urinated. Cystourethroscopy confirmed extensive intraurethral condylomatous lesions at the external urethral meatus. A biopsy revealed mild squamous dysplasia and cellular changes consistent with HPV infection. A treatment was prepared that included fluorouracil 250 mg combined with 0.18% lidocaine hydrochloride gel. This mixture was given intraurethrally once weekly, and the tip of the penis was clamped immediately after administration using an occlusive penile clamp. The clamp was retained for 10 minutes for the first treatment, 15 minutes for the second, and 20 minutes for the remainder of the treatments. Six treatments were given initially and were well tolerated, although the patient did report occasional pain while urinating and occasional drops of urine. After six weeks of rest, another cycle of six weekly treatments was given. Two weeks after the second course of treatment, one small condyloma was observed in the distal anterior urethra. The urethra was found to be unblocked after three months, and the six-month evaluation revealed no new growth and a clear urethra. CONCLUSION: Urethral instillation via urethral syringe of fluorouracil injection mixed with lidocaine gel reduced the size and number of a man's intraurethral condyloma acuminata, allowed cystourethroscopy, and eliminated hematuria. There was no new growth of condyloma acuminata after six months.

Managing reduced methotrexate clearance in a patient with a heterozygous methylenetetrahydrofolate reductase gene polymorphism.

High dose methotrexate has become one of the treatments of choice for patients with primary CNS lymphomas due to its ability to penetrate the blood-brain barrier. A potentially serious complication of this therapy is methotrexate-related nephrotoxicity. We report the case of a patient with a common genetic polymorphism that may have predisposed this patient experience clinically significant toxicity from systemic folate depletion. After the first cycle of chemotherapy that included high dose methotrexate, the patient's serum creatinine rose and the patient's methotrexate level remained above the toxic range for six days. On cycle two, the patient was treated with a 25% dose reduction in methotrexate and more aggressive hydration and alkalization. With this alteration in the regimen, the patient was able to receive six more cycles and had a complete radiographic tumor response in the brain and a disappearance of tumor cells in the CSF without any further renal complications. This case report illustrates the feasibility of administering high dose methotrexate with modifications as a treatment of choice in individuals with methylenetetrahydrofolate reductase gene mutations.