vary your genes if you cannot hand them on for the next generation to try out. Once reproduction is accomplished, however, it is of little
import to the species what happens to the ageing parent. The majority of malignant disease arises at just such a stage in the life cycle. Thus, if malignant disease is a byproduct of some intracellular mutagenic mechanism, it is an acceptable one from the evolutionary viewpoint. Indeed, it could even be better for the species as a whole. The individual, having done its reproductive best, quietly shuffles off its mortal coil and frees scarce resources for the next generation. Some thanks! For doctors (and patients) it is quite natural to view malignant disease as a nasty event. For biologists it is not. Malignant disease is disadvantageous to the individual but no bad thing for the species. Shotover Mound,
Spring Lane, Headington, Oxford OX3 8LG,
Ondansetron in intractable
therefore started as a last line of treatment at 8 mg intravenously twice daily. The response is shown in the figure. Ondansetron was accidently discontinued and the patient began vomiting profusely once more; ondansetron was restarted and the vomiting ceased. Once stable she was converted to oral ondansetron 8 mg twice daily on which she remained. She remained on dexamethasone throughout. Intractable nausea and vomiting is not uncommon in patients with cancer. The use of ondansetron in this setting is to be the subject of a clinical trial. Department of Medical Oncology, St George’s Hospital, London SW17 ORE, UK
1. Smith DB, Newlands ES, Rustin GJS, et al. A phase I/II study of the 5HT3 antagonist GR38032F in the antiemetic prophylaxis of patients receiving high dose cisplatin chemotherapy. Cancer Chemother Pharmacol 1990; 25: 291-94.
patients given abdominal radiotherapy
vomiting SiR,—The principal application for ondansetron to date has been antiemetic therapy for patients receiving chemotherapy, especially with platinum-based agents.1 We report on its use in a cancer patient with intractable nausea and vomiting which was not drug induced. A 42-year-old woman presented in January, 1991, with haematemesis and back pain. She had carcinoma of the breast with bony metastases (but no liver metastases), and endoscopy revealed monilial oesophagitis. She had a history of epilepsy, controlled on phenytoin and phenobarbitone. She was put on fluconazole and tamoxifen and referred for spinal irradiation. Whilst an inpatient at the radiotherapy centre she had two grand-mal convulsions associated with a subtherapeutic phenytoin level and hypomagnesaemia; a computer tomographic brain scan was normal. On return from the radiotherapy centre she entered a period of status epilepticus, from which she recovered well. 3 weeks later she began to vomit with increasing frequency and volume. Metabolic, infective, gastrointestinal, and central nervous system causes were excluded, as was drug-induced emesis (anticonvulsant levels within therapeutic range, dose of opioid analgesics progressively reduced). Standard antiemetics were used without benefit (figure). A nasogastric tube reduced the volume of vomit but did not alleviate nausea for the two days it remained in situ. The patient declined to have the tube re-inserted. Ondansetron is currently only recommended for nausea and vomiting induced by chemotherapy or radiotherapy and was as
DAILY TOTAL VOLUMES OF VOMITUS AND
SIR,-We report the effective use of oral ondansetron in patients receiving whole abdominal radiotherapy (WAR) with symptoms of emesis that were refractory to conventional antiemetic agents. A 36 kg, 9-year-old girl received WAR after debulking surgery for recurrent ovarian tumour with peritoneal spread. The dose was 30-4 Gy in 0-8 Gy fractions delivered twice daily. Prochlorperazine did not prevent emesis but oral ondansetron 8 mg thrice daily prevented nausea and vomiting, and the patient was able to engage in a complete range of activities, including swimming lessons, during her course of WAR. A 62 kg, 65-year-old woman received WAR for a recurrent ovarian adenocarcinoma with peritoneal spread found at debulking laparotomy. The dose was 30 Gy in 1Gy fractions once daily followed by cone-down fields. She vomited after radiotherapy when prochlorperazine was administered, but when given ondansetron 10 mg twice daily she was able to complete WAR without a break and without further epidoses of emesis. WAR is used to treat pelvic malignant disease, especially ovarian carcinoma. However, concerns about WAR, including the severe nausea and vomiting experienced by many patients given radiation therapy to the upper abdomen, have contributed to the limited use of this approach, despite renewed interest in its use for recurrent ovarian tumours.2,3 The nausea and vomiting associated with WAR often does not respond to conventional antiemetic agents, and when it is uncontrollable, radiotherapy may have to be interrupted. Ondansetron is effective for the prevention of chemotherapyassociated emesis but there are few reports on its efficacy in preventing radiation-associated nausea and vomiting. Although the intravenous route has been the recommended mode of administration in the USA, oral use of the intravenous formulation made up in juice has been described as successful in ameliorating chemotherapy-associated emesis.4 We are pleased to be able to record the efficacy of this formulation of the drug in radiation-associated emesis also. The oral route is important here because radiotherapy is usually given on an outpatient basis and the drug can be conveniently taken at home by mouth two or three times a day. We plan to use ondansetron not only during WAR but also for other patients with severe emesis during radiotherapy. The high cost of ondansetron precludes its use as first-line antiemetic therapy, but it should be considered for patients whose symptoms do not respond to other medications. UCSF/UCD Department of Radiation Oncology, Cancer Center, University of California, Davis, Sacramento, California 95817, USA 1.
volumes of vomitus and response to antiemetics.
STEPHEN NICHOLSON CHRISTOPHER EVANS JANINE MANSI
SETH A. ROSENTHAL CAROL M. MARQUEZ HELEN P. HOURIGAN JANICE K. RYU
Kidgell AE, Butcher ME, Brown GW Antiemetic control: 5-HT3 antagonists: review of clinical results, with particular emphasis on ondansetron. Cancer Treat Rev 1990;
17: 311-17. 2. Dembo AJ Radiotherapeutic management of ovarian cancer. Semin Oncol 1984; 11: 238-50. 3 Schray MF, Martinez A, Howes AE, et al. Advanced epithelial ovarian cancer: salvage whole abdominal irradiation for patients with recurrent or persistent disease after combination chemotherapy J Clin Oncol 1988; 6: 1443-49. 4. Oster MW. Oral ondansetron Ann Intern Med 1991; 115: 233.