HPV-Positive Oropharyngeal Cancer: The Nurse's Role in Patient Management of Treatment-Related Sequelae.

BACKGROUND: Patients diagnosed with oropharyngeal cancer (OPC) make up about 3% of all new cancer cases in the United States, with increasing numbers of these patients being diagnosed aged younger than 45 years and with human papillomavirus (HPV)-positive disease. Treatment effects may alter patients' physical and mental states during and after treatment. OBJECTIVES: This article provides an overview of possible OPC treatment long-term effects to equip oncology nurses with information needed to empower patients with OPC to perform self-care. METHODS: The OPC literature was reviewed to identify incidence, survival, risk factors, symptoms, treatment options, and treatment effects. FINDINGS: This article provides a foundation for the plan of care for patients with OPC and strategies for patients to contribute to their self-care.

Two drug interaction studies evaluating the pharmacokinetics and toxicity of pemetrexed when coadministered with aspirin or Ibuprofen in patients with advanced cancer.

PURPOSE: Pemetrexed is an antimetabolite that is structurally similar to methotrexate. Because nonsteroidal anti-inflammatory drugs (NSAID) impair methotrexate clearance and increase its toxicity, we evaluated the pharmacokinetics and toxicity of pemetrexed when coadministered with aspirin or ibuprofen in advanced cancer patients. EXPERIMENTAL DESIGN: In two independent, randomized, crossover drug interaction studies, cancer patients with a creatinine clearance (CrCl) > or =60 mL/min received an NSAID (aspirin or ibuprofen) with either the first or the second dose of pemetrexed (cycle 1 or 2). Pemetrexed (500 mg/m(2)) was infused i.v. on day 1 of a 21-day cycle, and all patients were supplemented with oral folic acid and i.m. vitamin B(12). Aspirin (325 mg) or ibuprofen (400 mg; 2 x 200 mg) was given orally every 6 hours, starting 2 days before pemetrexed administration, with the ninth and final dose taken 1 hour before infusion. Pemetrexed pharmacokinetics with and without concomitant NSAID treatment were compared for cycles 1 and 2. RESULTS: Data from 27 patients in each study were evaluable for the analysis of pemetrexed pharmacokinetics. Coadministration of aspirin did not alter pemetrexed pharmacokinetics; however, ibuprofen coadministration was associated with a 16% reduction in clearance, a 15% increase in maximum plasma concentration, and a 20% increase in area under the plasma concentration versus time curve but no significant change in V(ss) compared with pemetrexed alone. No febrile neutropenia occurred in any patient, and no increase in pemetrexed-related toxicity was associated with NSAID administration. CONCLUSIONS: Pemetrexed (500 mg/m(2)) with vitamin supplementation is well tolerated and requires no dosage adjustment when coadministered with aspirin (in patients with CrCl > or =60 mL/min) or ibuprofen (in patients with CrCl > or =80 mL/min).

A Phase I trial of a potent P-glycoprotein inhibitor, zosuquidar trihydrochloride (LY335979), administered intravenously in combination with doxorubicin in patients with advanced malignancy.

PURPOSE: Our intention was to (a) to investigate the safety and tolerability of a potent P-glycoprotein modulator, zosuquidar trihydrochloride (LY335979), when administered i.v. alone or in combination with doxorubicin, (b) to determine the pharmacokinetics of zosuquidar and correlate exposure to inhibition of P-glycoprotein function in a surrogate assay, and (c) to compare the pharmacokinetics of doxorubicin in the presence and absence of zosuquidar. PATIENTS AND METHODS: Patients with advanced malignancies who provided written informed consent received zosuquidar and doxorubicin administered separately during the first cycle of therapy and then concurrently in subsequent cycles. Zosuquidar was given i.v. over 48 h in a cohort-dose escalation manner until the occurrence of dose-limiting toxicity or protocol specified maximum exposure. Doxorubicin doses of 45, 60, 75 mg/m(2) were administered during the course of the trial. RESULTS: Dose escalation proceeded through 9 cohorts with a total of 40 patients. The maximal doses administered were 640 mg/m(2) of zosuquidar and 75 mg/m(2) of doxorubicin. No dose-limiting toxicity of zosuquidar was observed. Pharmacokinetic analysis revealed that, in the presence of zosuquidar at doses that exceeded 500 mg, there was a modest decrease in clearance (17-22%) and modest increase in area under the curve (15-25%) of doxorubicin. This change was associated with an enhanced leukopenia and thrombocytopenia but was without demonstrable clinical significance. The higher doses of zosuquidar were associated with maximal P-glycoprotein inhibition in natural killer cells. CONCLUSION: Zosuquidar can be safely coadministered with doxorubicin using a 48 h i.v. dosing schedule.