Reduced Dose Zofran Appears Effective as Pediatric Antiemetic

April 1, 1995

ALBUQUERQUE--Oncologists and pharmacists at the University of New Mexico initially turned to reduced-dose ondansetron (Zofran) for their pediatric leukemia patients for sheer expediency--most of the children were receiving their

ALBUQUERQUE--Oncologists and pharmacists at the University ofNew Mexico initially turned to reduced-dose ondansetron (Zofran)for their pediatric leukemia patients for sheer expediency--mostof the children were receiving their chemotherapy as outpatientsand were only in the clinic for about 4 hours per treatment.

This made it impossible to give the recommended intravenous ondansetrondosage of 0.15 mg/kg every 4 hours for three doses during theoutpatient visit.

"We settled on two doses and demonstrated efficacy for quitea few chemotherapy protocols, with a very good side effect profile,"Mark T. Holdsworth, PharmD, assistant professor, College of Pharmacy,University of New Mexico, told Oncology News International inan interview.

The New Mexico investigators evaluated 255 courses of emetogenicchemotherapy in 16 pediatric outpatients with ALL. No antiemetictherapy was administered with 149 courses (primarily because,before ondansetron became available, patients often refused antiemetictherapy due to lack of perceived benefit). Two doses of IV ondansetron,0.15 g/kg, were given with 106 courses, one dose prior to andone dose immediately following each course.

Fourteen patients received an intensive ALL regimen with bothIV and intrathecal chemotherapy, and two patients received a low-riskALL regimen with only intrathecal treatments.

Intrathecal therapy consisted of methotrexate, hydrocortisone,and cytarabine. Patients on intensive regimens also received sequentialIV courses of cyclophosphamide (Cytoxan, Neosar), daunorubicin(Cerubidine), carmustine (BiCNU), and a combination of cytarabineand etoposide (VePesid).

Ondansetron provided complete protection against nausea and vomitingfor more than 60% of the courses of carmustine and etoposide/cytarabine,and complete protection against vomiting for more than 55% ofthe courses of cyclophosphamide, Dr. Holdsworth said. These agentsor combinations represent three of the four most emetogenic treatmentsexamined in the study.

Not enough courses of both ondansetron and daunorubicin or intrathecalchemotherapy were completed for analysis of effectiveness withthese agents, Dr. Holdsworth said.

Based on these results, published in the Annals of Pharmacotherapy(29:16-21, 1995), Dr. Holdsworth and his colleagues in the studybelieve that the abbreviated dosing schedule may have importantpractical applications, given its efficacy, safety, convenience,and potential cost savings.

Dr. Holdsworth's co-investigators were Dennis W. Raisch, PhD;Marilyn H. Duncan, MD; Cathy M. Chavez, BSN; and Mary M. Leasure,BSN, all of the University of New Mexico.

Some Still Need Full Dose

"We don't use this reduced-dose regimen for all our kidson chemotherapy," Dr. Holdsworth emphasized. "For thosepatients receiving chemotherapy known to cause severe vomiting,we still give full doses, but in other settings--not as outpatientsin the clinic," he said.

The University has contracted with local home-care agencies todeliver medications in the home, which is more acceptable forthe families, he pointed out.

Dr. Holdsworth feels that ondansetron might also have advantagesin other treatment settings. "There is some published datashowing that ondansetron and some of the newer 5-HT3 analogs arealso effective in reducing emesis resulting from radiation therapy,especially to the abdomen," he commented. [Oral ondansetron(Zofran Tablets) has just received FDA approval for this indication.

At the University of New Mexico, ondansetron has been given tochildren receiving abdominal radiation, and has "pretty muchstopped the vomiting--but we don't have enough cases or a lotof data yet," he said.

Routine Monitoring Essential

Dr. Holdsworth noted that there is "quite a bit of debateand confusion regarding which dose of ondansetron to use--or whetherto use other newer drugs," with decisions on drugs and dosagesoften made rather capriciously rather than based on data.

Unfortunately, he said, many centers do not routinely monitornausea/vomiting with good surveys on every patient receiving chemotherapyevery time the patient comes in. "This must be done if weare to learn how to use these agents most effectively."

Such surveys are done at the University of New Mexico, Dr. Holdsworthsaid, and are currently showing very good control of nausea/vomitingin approximately 90% of patients.

"If some day we switch to a different antiemetic regimen,we will be able to determine whether we are still doing a goodjob or if our efficacy is falling off," he said. "I'dlike to see most centers start using that approach. It takes careof patients as well as supplying data."