Search

Patients with locally advanced stage 3 or 4 recurrent squamous cell carcinoma of the head and neck received 5-fluorouracil (5-FU) 200 or 300 mg/m2/day by prolonged ambulatory infusion concomitantly with radiotherapy (60-66 Gy) to the primary site and neck nodes in 30-33 fractions at five fractions per week, boosting to smaller volumes after 60 Gy. Of 39 patients, the complete response rate was 82% (95% CI: 67-93%). The estimated percentage without failure at 2 years was 59% (S.E. 8%) and at 4 years was 50% (S.E. 8%). Estimated head and neck cancer specific survival was 64% (S.E. 8%) at 2 years and 52% (S.E. 8%) at 4 years. Acute toxicities included moist desquamation in 49% and dry desquamation in 28%, confluent mucositis in 56% and patchy mucositis in 44%. Late effects, more than 6 months after completing treatment, assessed in 35 patients, included severe salivary dysfunction in 3 patients and moderate in 21, severe osteonecrosis in 4 patients and moderate toxicity in subcutaneous tissues in 13, skin in 3 and mucosa in 2 patients. It is feasible to give continuous 5-FU concurrently with radiotherapy in locally advanced or recurrent head and neck cancer, albeit with increased toxicity. The response rate and survival obtained in this trial justify further investigation of the combined treatment in a randomised trial.

Patients receiving outpatient chemotherapy, without cisplatin, were randomised to receive four doses of either domperidone 60 mg or prochlorperazine 25 mg suppositories every 4 h, starting 30 min before the chemotherapy. They were crossed over for the next chemotherapy cycle. To enable analysis of 100 patients who had received identical chemotherapy in each course, 136 patients were randomised. Patients experienced a higher grade of nausea on domperidone (P = 0.05). Only 18% of patients vomited on domperidone and 14% on prochlorperazine, but the number of vomits was higher on domperidone (P = 0.003) and the duration was significantly increased (P = 0.02). Patients experienced significantly more diarrhoea on domperidone (P < 0.0001), although it was predominantly mild. Patients were significantly more sedated on prochlorperazine on the second course (P = 0.006), but not on the first course (P = 0.9). More patients preferred their second course (P < 0.0001), and were significantly less anxious (P = 0.0002). Patients reported tolerating their treatment similarly for both antiemetics, but more patients preferred prochlorperazine (P = 0.003), mainly due to reductions in nausea and vomiting and other side-effects, particularly diarrhoea.

The endpoints assessed by both patients and nurses were compared in three anti-emetic studies. In a parallel subjects study, there was no significant difference between the patients' and nurses' assessment of the number of vomiting episodes, but the duration of vomiting, the severity and duration of nausea, and the side-effects of the anti-emetic were given higher scores by the nurses. In two cross-over studies, the patients recorded more vomiting episodes than the nurses, while the nurses recorded more anxiety and sedation than the patients. This resulted in the patients detecting a difference between the side-effects of the anti-emetics being compared that was not apparent from the nurses' forms. Many of the differences reflect differences in the timing and frequency of data collection. Nurses collected data regularly during the assessment period whereas patients reported their experiences only at the completion of 24 h. Both assessments provide useful perspectives on the study outcomes.

To assess the effect of danazol in advanced breast cancer 183 patients were randomised to receive either tamoxifen plus danazol or tamoxifen plus placebo. Patients underwent systemic work-up pretreatment then every 12 weeks or sooner if they clinically progressed. There were no differences in objective response rates with tamoxifen plus danazol vs. tamoxifen plus placebo (27% vs. 24%), time to progression (median 6.4 vs. 6.2 months) or survival (median 22.6 vs. 23.5 months) when the two arms were compared (all P > 0.5). The addition of danazol to tamoxifen had no effect on time to progression when adjusted for significant prognostic factors in a multivariate analysis. However, it was found incidentally that weight was stable on tamoxifen plus danazol (average gain 0.6 kg, S.E. 0.6 kg) compared with a significant loss on tamoxifen plus placebo (average loss 2.0 kg, S.E. 0.6 kg, P = 0.003). The average weight was maintained on tamoxifen plus danazol even in patients who did not respond to treatment.

To define further the place of dexamethasone in antiemetic combinations, lorazepam, prochlorperazine and placebo (LP) were compared with lorazepam, prochlorperazine and dexamethasone (DLP) in a randomised, double-blind, crossover study. Both patient and observer assessments were documented in 84 patients receiving both cisplatin and non-cisplatin chemotherapy. The addition of dexamethasone significantly reduced the severity of nausea (P = 0.002) and vomiting (P less than 0.0001), duration of nausea (P = 0.01) and vomiting (P = 0.002) and the number of vomiting episodes (P = 0.003). DLP was the superior regimen in subsets of patients receiving cisplatin and the non-cisplatin chemotherapy. The improvements produced by the dexamethasone regimen were large and of major benefit to our patients. Patients documented significantly improved tolerance to chemotherapy with DLP courses (P = 0.0006). Overall, significantly more patients preferred DLP (P less than 0.0001). Patient assessments produced results similar to observer assessments but gave a broader understanding of their experience. The addition of dexamethasone to prochlorperazine and lorazepam significantly improved our patients' experience while receiving chemotherapy.

High-dose prochlorperazine 0.8 mg/kg administered intravenously 30 min pre and 7 h 30 min post the initial dose of emetogenic chemotherapy was compared to high-dose metoclopramide 2 mg/kg over 20 min every 2 h for five doses starting 30 min prior to chemotherapy in a randomised, double-blind, parallel subjects design study. On the prochlorperazine arm intravenous dextrose placebos every 2 h maintained blinding. Complete suppression of vomiting occurred in 42% on metoclopramide (53% with non-cisplatin regimens) and 36% on prochlorperazine (52% with non-cisplatin-containing regimens) while major responses (2 or less vomits) occurred in 58% on metoclopramide and 54% on prochlorperazine. In patients who vomited after cisplatin, prochlorperazine achieved a significantly shorter duration of vomiting, a median of 5 h compared to 15 h on metoclopramide (P = 0.03). The response rate to prochlorperazine for cisplatin-induced emesis between 12 and 24 h was significantly better than for metoclopramide (prochlorperazine = 0.02). Toxicities were equivalent except for significantly greater sedation and dry mouth on prochlorperazine. Extrapyramidal reactions were recorded equally on both arms but were only severe enough to stop treatment on metoclopramide. The metoclopramide regimen was five times as expensive as prochlorperazine. High-dose prochlorperazine is an active and cost-effective antiemetic.