The clinical use of ondansetron. New South Wales Therapeutic Assessment Group.

OBJECTIVE: To establish guidelines for use of ondansetron. DATA SOURCES: MEDLINE computer search (to July 1993) and information from the manufacturer. DATA EXTRACTION: We circulated a position paper based on our literature review for comment by clinicians and directors of pharmacy in major teaching hospitals in New South Wales who had an interest in ondansetron. DATA SYNTHESIS: Ondansetron is effective in the control of nausea and vomiting occurring 24-48 hours after highly emetogenic chemotherapy and after radiotherapy. There are no data to support its use in delayed emesis. Combination with dexamethasone may improve emetic control. The most commonly reported adverse effects are headache and constipation. Optimal dose, frequency of dosing and route of administration have not been established. The cost for each inpatient treated successfully is about 3% more than conventional antiemetic therapy. CONCLUSIONS: Ondansetron shows clinical benefit in the management of acute nausea and vomiting in patients receiving highly emetogenic chemotherapy, those who have responded poorly to other antiemetics after moderately emetogenic chemotherapy, those who have intolerable side effects with conventional antiemetic agents and those receiving radiotherapy to the upper abdomen. It is also marketed for the prevention and treatment of postoperative nausea and vomiting.

Prediction of life-expectancy in hospice patients: identification of novel prognostic factors.

The prediction of life-expectancy in terminally ill patients is important both for medical and social reasons but is widely recognized as being inaccurate. In this study we prospectively collected data items which we proposed might influence survival on 148 consecutive patients at first admission to one of two hospices. Of the 19 parameters collected, four were associated with a significantly shortened survival. These were low performance status (PS), requirement for admission at first referral to the palliative care service, elevated serum bilirubin, and hypotension. Factors previously identified as predictive of shortened survival such as hyponatraemia, weight loss, confusion and tumour type were not confirmed as statistically significant independent variables. We plan to collect these data items on future patients in order to test the validity of these results.

The clinical application of the interferons: a review. NSW Therapeutic Assessment Group.

OBJECTIVES: To review the clinical information on the use of alpha, beta and gamma interferons and to classify the use of alpha interferons in Australia according to approved indications, indications for which there is good supporting evidence and indications where therapy is under investigation; and to estimate the cost of therapy with alpha interferons in New South Wales in 1991. DATA SOURCES: Data were obtained from computerised literature searches. DATA EXTRACTION: A position paper was drafted on behalf of the NSW Therapeutic Assessment Group (NSWTAG). This was circulated to clinicians identified as having a particular interest in the use of the interferons in major NSW teaching hospitals, for comment and amendment where necessary. CONCLUSIONS: Two forms of alpha interferon, interferon alfa-2b and interferon alfa-2a have been approved for use in Australia, interferon alfa-2b for use in the management of hairy cell leukaemia and condylomata acuminata and interferon alfa-2a for use in the management of hairy cell leukaemia and human immunodeficiency virus (HIV) related Kaposi's sarcoma. Applications have been lodged for the use of interferon alfa-2b in HIV related Kaposi's sarcoma, cutaneous basal cell carcinoma and hepatitis B and C and for the use of interferon alfa-2a in the management of hepatitis B, cutaneous T-cell lymphoma and metastatic renal cancer. Interferon alfa-n1 is not available in Australia except for use in a clinical trial in patients who are HIV seropositive. The use of the alpha interferons is currently under investigation in a wide variety of other diseases, with the likelihood that other indications will soon be established. However, the alpha interferons are generally not regarded as first line agents. Beta and gamma interferons have been studied less intensively than the alpha interferons, but it is likely that selected applications for their use will also be defined with the passage of time.

The cost of treating small cell lung cancer.

OBJECTIVE: To determine the cost of treating small cell lung cancer (SCLC) and to assess quality-adjusted survival in these patients. DESIGN: Retrospective analysis. SETTING: Westmead Hospital, a tertiary referral institution. PATIENTS: Consecutive sample of 31 patients with histologically proved SCLC, treated between January 1987 and December 1987. MAIN OUTCOME MEASURES: The cost of investigation, hospitalisation, chemotherapy, radiotherapy and follow-up of patients overall and for those with limited and extensive disease respectively. Quality-adjusted survival was based on a Q-TWiST analysis. RESULTS: The median overall cost per patient was $14,413 (range, $1188-$39,598) for all patients and for limited disease and extensive disease was $18,234 (range, $1914-$39,598) and $13,177 (range, $1188-$32,798) respectively. The two major costs were hospitalisation (42%) and chemotherapy (18%). Radiotherapy accounted for 11% of all costs. The Q-TWiST analysis suggests that for patients with limited disease, quality-adjusted survival is similar to absolute survival. CONCLUSIONS: The treatment of SCLC at our institution was expensive but the cost may be reduced by reduction in the duration of hospitalisation, the use of less expensive combination drug regimens, or the use of "true" outpatient chemotherapy. Despite intensive therapy, patients with limited disease maintained a reasonable quality of life.

Single institutional experience with non-seminomatous germ cell tumours of the testis: local perspectives on a curable cancer.

We have reviewed 77 patients with Non-seminomatous germ cell tumour of the testis (NSGCTT) treated at a single institution. A residual mass following definitive treatment occurred in 16 patients (35%), 13 of whom had a resection of the mass, yielding active tumour in only one patient. Nine patients (12%) relapsed including four of the 14 with Stage I disease who were treated by orchidectomy alone. Four relapses occurred at more than two and a half years after primary treatment. Relapse prior to the development of clinical symptoms or signs was evident in three of nine patients; in two patients by routine imaging and one with elevated routine serum markers. Three of the nine patients who relapsed had elevated serum markers. Two patients died from disease but there were four treatment-related deaths (7%). Overall, 64 patients (83%) remain disease free at the time of follow-up. A further seven (9%) have been lost to follow-up but were disease-free at a minimum of 26 months after diagnosis. This study confirms features of this disease including the excellent prognosis when adequately treated. However, it also reveals the problems of late or marker negative relapses, the implementation of an observation policy in Stage I disease and treatment related mortality in young men.

Mitoxantrone for the treatment of advanced breast cancer: single-agent therapy in previously untreated patients.

Mitoxantrone (dihydroxyanthracenedione) is a substituted anthraquinone with a similar spectrum of activity to adriamycin in experimental tumours. One hundred and thirty-four patients with advanced breast cancer and no prior chemotherapy for advanced disease were treated with mitoxantrone (14 mg/m2 i.v. q 3 weeks), of whom 99 are presently evaluable for response and all for toxicity. Six patients achieved a complete response and 29 a partial response, the overall response rate being 35% (95% confidence limits, 25-45%). Median time to treatment failure was greater than 46 weeks. Mitoxantrone was well tolerated, myelosuppression being the dose-limiting toxicity. The most frequent nonhaematological toxicities were nausea and vomiting (40%), but these were rarely severe. Total alopecia occurred in only 6 patients. Four patients developed clinically significant evidence of cardiotoxicity after cumulative mitoxantrone doses of 174-256 mg/m2. Mitoxantrone offers comparable efficacy and less acute toxicity than the most active currently available single agents in advanced breast cancer.

Mitoxantrone as first-line chemotherapy for advanced breast cancer: results of a European collaborative study.

A total of 134 patients with advanced breast cancer and no prior chemotherapy for advanced disease were treated with mitoxantrone, 14 mg/m2 intravenously every 3 weeks. Of these, 99 could be evaluated for response and all for toxicity. Six patients achieved a complete response and 29 a partial response, the overall response rate being 35% (95% confidence limits 25% to 45%). The median time to treatment failure was greater than 46 weeks. Mitoxantrone was well tolerated. Nausea and vomiting occurred in 40% of patients, but these were seldom severe. Total alopecia occurred in only six patients. Four patients developed clinically significant evidence of cardiotoxicity after cumulative doses of 174 to 256 mg/m2. Mitoxantrone offers comparable efficacy and less acute toxicity than the most active single agents currently used in the treatment of advanced breast cancer.

Mitoxantrone: an active new agent in the treatment of advanced breast cancer.

Sixty-five patients with advanced breast carcinoma were treated with mitoxantrone, an anthracenedione with structural similarities to adriamycin. The series included 26 patients who had received no prior chemotherapy. Treatment was given in a dose of 12-14 mg/m2 by IV infusion, repeated every 3 weeks. Sixty-two patients were evaluable for response, but all were evaluable for toxicity. One (2%) achieved a complete response and 18 (29%) a partial response (overall response rate 31%). The response rate in patients who had received no prior chemotherapy was 35%, vs 22% in previously treated patients. The median duration of response was 10 months (range 3.5-18.5 months). Two responders had previously failed to respond to adriamycin, and a third responder subsequently failed to respond to adriamycin. Neutropenia was the most frequently seen toxicity, with a WBC of less than 2,000/mm3 seen in 26 patients (40%), eight of whom (12%) had a neutropenic infection. Thrombocytopenia (less than 100,000/mm3) occurred in 12 patients (18%), but in three of these only after at least 6 months of treatment. Two patients developed readily reversible cardiac failure after prolonged treatment (11-13 months). Other toxicities were in general mild, and the drug was well tolerated: severe alopecia occurred in only one patient. Mitoxantrone is an active well-tolerated agent in the treatment of advanced breast carcinoma, but the risk of neutropenia requires careful supervision. The long-term risk of cardiotoxicity cannot yet be fully assessed.

Small-cell lung carcinoma: survival after combination chemotherapy, radiotherapy or symptomatic treatment.

A retrospective comparison was made of the survival of patients with small-cell lung carcinoma treated by combination cytotoxic chemotherapy (CT), radiotherapy (RT) or symptomatic therapy alone (ST). Forty-three patients received CT and 42 patients of similar age and performance status each received RT or ST at the same group of hospitals. The median survival was 43 weeks with CT, 18 weeks with RT and 6 weeks with ST and 1 year survivals of 36%, 12% and 8% respectively were obtained. Despite the limitations of a retrospective study these results suggest that an improved survival with toxicity acceptable to most patients results from cytotoxic chemotherapy.

Levonantradol: a synthetic cannabinoid in the treatment of severe chemotherapy-induced nausea and vomiting resistant to conventional anti-emetic therapy.

Twenty-three patients with severe nausea and vomiting refractory to conventional anti-emetic therapy were entered into an open phase II study of levonantradol. Of 22 patients evaluable for response, three achieved complete relief from nausea and vomiting, seven obtained very good relief from nausea and vomiting, four obtained a partial reduction in nausea and vomiting, and eight obtained no relief. However all patients experienced side effects including, in particular, drowsiness and thought disturbance, and as a result eight patients had to be withdrawn from the study. There was no statistical patient preference for levonantradol over previous anti-emetic treatment. Levonantradol is an effective anti-emetic in approximately 50% of patients resistant to conventional anti-emetics; however, its usefulness is likely to be restricted by side effects which are common and frequently unpleasant.

High-dose alkylation therapy using ifosfamide infusion with mesna in the treatment of adult advanced soft-tissue sarcoma.

In a phase II study, 42 patients with advanced soft-tissue sarcoma were treated with ifosfamide by 24-h infusion and mesna by 4-h IV bolus, repeated every 3 weeks. Ten patients received ifosfamide 5.0 g/m2, 20 had the dosage increased to 8.0 g/m2, and 12 received 8.0 g/m2 from the outset. Mesna was given in doses of 400 mg/m2 or 600 mg/m2. Of 40 patients evaluable for response, six (15%) achieved complete response and nine (23%) partial response. The overall response rate was 38%. The median duration of response was 11 months. Treatment was associated with falls in peripheral WBC and alopecia in all patients. Most experienced severe nausea and vomiting. In seven nephrotoxicity developed, and two of these died of renal failure. Renal tubular defects and cerebral effects also occurred. Mesna largely prevented haemorrhagic cystitis. Ifosfamide offers a new alternative to previous chemotherapy for advanced soft-tissue sarcoma, but alterations in dose or method will be necessary to reduce toxicity.

Mitoxantrone: a phase II study in the treatment of patients with advanced breast carcinoma and other solid tumours.

A phase II study of mitoxantrone, an anthraquinone derivative with structural similarities to adriamycin, has been carried out in 34 patients with advanced breast carcinoma and other malignancies. The first 20 patients were treated with a starting dose of 12 mg/m2 by IV infusion repeated every 3 weeks; this was escalated to 14 mg/m2 in the subsequent 14 patients. Of the 29 patients with advanced breast carcinoma, 8 achieved a partial response and two further patients achieved a mixed response. There were no complete responses. Of the eight responding patients, five had received no prior chemotherapy. Response duration ranged from 3 1/2 months to 10+ months. No responses were seen in the other five patients, three whom had small cell carcinoma of the lung, and one colonic carcinoma. Neutropenia was the most frequently seen toxicity but was usually mild and transient; WBC fell to less than 2,000/mm3 in eight patients and to less than 1,000/mm3 in only two. Otherwise, the drug was well tolerated; nausea occurred in 35% of patients and vomiting in 21%; severe alopecia requiring a wig was never seen. Mitoxantrone appears to be a well-tolerated and clinically active agent against advanced breast carcinoma.