Novel oral fluoropyrimidines in the treatment of metastatic colorectal cancer.

The evolution of and rationale for fluorouracil-based strategies in the treatment of metastatic colorectal cancer are discussed, and the role of the new oral fluoropyrimidines is described. Although fluorouracil is one of the most widely used drugs in the United States for colorectal, head and neck, bladder, and breast cancer, response rates and survival times have been disappointing. Dihydropyrimidine dehydrogenase (DPD), a rate-limiting enzyme in the catabolism of fluorouracil, indirectly determines the drug's anticancer efficacy by regulating the availability of fluorouracil for anabolism. Recently, investigators have identified at least five compounds -capecitabine, UFT (tegafur plus uracil), eniluracil, S-1, and BOF-A2-that inhibit, destroy, inactivate, or bypass DPD's activity. Capecitabine, a prodrug of fluorouracil, circumvents DPD. UFT, S-1, and BOF-A2 contain prodrugs of fluorouracil in combination with compounds that alter DPD's activity. Fluorouracil must be administered in combination with eniluracil, an inactivator of DPD. These compounds, classified as fluoropyrimidines, can be administered orally. Oral fluoropyrimidines appear to be at least as active against metastatic colorectal cancer as conventionally administered intravenous fluorouracil, with significantly less toxicity, improved quality of life, and less expense. New oral fluoropyrimidines may ultimately provide enhanced antitumor activity to fluorouracil-containing regimens for advanced colorectal cancer.

The PRO-SELF Mouth Aware program: an effective approach for reducing chemotherapy-induced mucositis.

Many oncology patients receive chemotherapy drugs that have the potential to induce oral mucositis. If mucositis is not prevented, patients will have to manage the problems associated with mucositis: pain, local infection, and decreased ability to take fluids or food. At the time of this writing, clinical approaches for mucositis management are variable and generally ineffective. The mouth care program, PRO-SELF: Mouth Aware (PSMA), presented in this article, was found to be a significant component of a self-care program that may have reduced the incidence of chemotherapy-induced mucositis. The PSMA program has three dimensions: (a) didactic information, (b) development of self-care exercises (skills), and (c) supportive interactions with a nurse in the setting where the patients are receiving their treatment. This program focuses on decreasing the direct (i.e., incidence and severity of mucositis) and indirect morbidities of oral mucositis (i.e., number of local infections, level of discomfort/pain, and disruption in fluid and/or food intake). It provides the critical dimensions (i.e., specific information, self-care exercises, and nurse support) to promote the prevention of mucositis. The PSMA program is designed to provide patients with a definitive self-care repertoire to manage chemotherapy-induced mucositis in the home without the direct supervision of a health care provider.

Docetaxel in anthracycline-resistant metastatic breast cancer.

Docetaxel is a taxane that disrupts the equilibrium in the polymerization and depolymerization of microtubules, thus inhibiting cell growth. This agent is indicated for the treatment of anthracycline-resistant metastatic breast cancer. The dose-limiting adverse effect is neutropenia, but febrile neutropenia is uncommon. Like paclitaxel, docetaxel is very active in patients with both chemotherapy-resistant and refractory metastatic breast cancer. Although the mechanism of action, spectrum of activity, and side effect profile of this agent are similar to those of paclitaxel, docetaxel may be efficacious in patients with metastatic breast cancer who have become resistant or refractory to paclitaxel therapy. However, more studies are warranted before the role of docetaxel is defined in patients with paclitaxel-resistant breast cancer.

Randomized clinical trial of chlorhexidine versus placebo for prevention of oral mucositis in patients receiving chemotherapy.

PURPOSE/OBJECTIVES: To test the effectiveness of a nurse-initiated systematic oral hygiene teaching program-PRO-SELF: Mouth Aware (PSMA)-in conjunction with two mouthwashes (0.12% chlorhexidine or sterile water) in preventing chemotherapy-induced oral mucositis. DESIGN: Randomized, double-blind, placebo-controlled, clinical trial. SETTINGS: 23 outpatient clinics and office practices in California. SAMPLE: 222 patients who were starting a cycle of mucositis-inducing chemotherapy. METHOD: Participants were followed over three chemotherapy cycles. All patients were provided the PSMA program. Random assignment to a mouthwash occurred prior to the development of oral mucositis. Researchers used the Oral Assessment Guide to assess the patients oral cavities monthly (with the patients cycles of chemotherapy) and when patients reported any oral changes between cycles. MAIN RESEARCH VARIABLES: Type of mouthwash, incidence, days to onset, and severity of chemotherapy-induced oral mucositis. FINDINGS: No significant differences existed between the two mouthwashes in regard to incidence, days to onset, and severity of mucositis. CONCLUSIONS: Because chlorhexidine (S20 per pint) was no more effective than water, a substantial cost savings can be realized by rinsing with water. Interestingly, the PSMA program appeared to reduce the incidence of mucositis from on a prior estimate of 44% to less than 26%. IMPLICATIONS FOR NURSING PRACTICE: A nursing prescription of a systematic oral hygiene program using water as a mouth rinse is cost efficient and may be effective in preventing oral mucositis.

If there are expert systems and dose checks, why do we still need the clinical pharmacist?

Trends in patient care, along with escalating health care costs, and the demand for medication safety may provide a breadth of opportunities for clinical pharmacists. Service and drug use guidelines development, medication error prevention, quality assurance, and pharmacoeconomic assessment are areas in which skills of the oncology pharmacist may be used. Although expert systems may aid the pharmacist in these areas, such systems cannot replace the professional.

Granisetron.

Granisetron is the second agent in the 5-HT3 receptor antagonist class to be approved for the prophylaxis of acute emesis caused by cancer chemotherapy. It is equally effective to ondansetron as a first-line agent in the prevention of acute chemotherapy-induced emesis and has a similar low toxicity profile. Granisetron will be marketed in early 1994, according to SmithKline Beecham. Additional studies will be needed to determine the role of granisetron in the current management of chemotherapy-induced emesis.

Parenteral nutrition support in patients with cancer.

In the patient with cancer, malnutrition may result from the disease itself or from its treatment. Total parenteral nutrition (TPN) has been used for many years to treat or prevent malnutrition in the patient with cancer. There have been few studies, however, that demonstrate significant benefit from TPN therapy in these patients. Patients receiving high-dose chemotherapy (as in bone marrow transplantation), and patients with solid tumors who have documented malnutrition (cachexia, weight loss) prior to cancer surgery, may benefit from TPN. No other groups of patients with cancer appear to derive significant benefit from TPN, and some groups may actually be harmed by its use. Practical considerations in the use of TPN include periodic calorie-protein assessment, electrolyte management, and monitoring for drug-TPN interactions.