Testosterone deficiency and quality of life in Australasian testicular cancer survivors: a prospective cohort study.

This is the first prospective study in a contemporary Australian/New Zealand population to determine the prevalence of testosterone deficiency in testicular cancer survivors at 12 months from treatment, and any association with poorer quality of life. Hormone assays from 54 evaluable patients in a prospective cohort study revealed biochemical hypogonadism in 18 patients (33%) and low-normal testosterone in 13 patients (24%). We found no association between testosterone levels and quality of life (all P > 0.05). Hypogonadal patients should be considered for testosterone replacement to prevent long-term morbidity.

Results of a 7-day aprepitant schedule for the prevention of nausea and vomiting in 5-day cisplatin-based germ cell tumor chemotherapy.

PURPOSE: The purpose of this study was to determine the efficacy of adding a 7-day aprepitant schedule to a 5HT3 receptor antagonist and dexamethasone for patients with germ cell tumors receiving first-line 5-day cisplatin-based chemotherapy. METHODS: In a single-arm, open-label, multi-center, phase 2 trial, chemo-naive patients received aprepitant 125 mg PO (per oral) on day 1 and 80 mg PO on days 2 to 7, a 5HT3 receptor antagonist on days 1 to 5, and dexamethasone 8 mg on days 1 to 8. The primary endpoint was no emesis (vomiting or dry retching) during days 1 to 7 of cycle 1. RESULTS: Fifty patients were recruited. For cycle 1, proportions reporting no emesis on day 1, no emesis on days 1 to 7, no nausea on day 1, and no nausea on days 1 to 7 were 96, 82, 71, and 27%, respectively. The efficacy was maintained in all cycles with over 80% of patients reporting no emesis on any given day of any given cycle. Emesis was more common on days 4 to 7 (68% episodes) than on days 1 to 3 (32% episodes). Over any 24-h period, 49% of patients with emesis reported no more than two episodes, and 62% of patients with nausea reported intensity as 3 or less on a scale from 0 to 10. There were no unexpected or serious adverse events reported. CONCLUSION: Adding 7 days of aprepitant to a 5HT3 receptor antagonist and dexamethasone effectively controlled acute and delayed emesis with 5-day cisplatin regimens. Days of nausea were more common than days of vomiting.

Prevalence and predictors of complementary and alternative medicine (CAM) use by men in Australian cancer outpatient services.

BACKGROUND: Although studies have shown that complementary and alternative medicine (CAM) use is common in cancer patients, no survey has assessed CAM use in men with a variety of cancers. In Australia, no data exist about male cancer patients' use of CAM. PATIENTS AND METHODS: A self-administered questionnaire was completed by 403 men attending four cancer outpatient services in Metropolitan Adelaide. Data were analyzed using Pearson's χ(2) tests and multivariate logistic regression analysis. RESULTS: CAMs were currently used by 52.9%, or used at some point by 61.5%, of respondents. The most popular CAM treatments were dietary supplements (36.1%), prayer (25.9%), herbs and botanicals (21.4%), and relaxation techniques/meditation (15.2%). CAM use was directed by a cancer specialist in 9.9% of respondents. Independent predictors of CAM use were metastatic cancer (P = 0.022), actively practicing religion (P = 0.008), and tertiary education (P = 0.007). CONCLUSIONS: CAM use in males is equally common across all cancer diagnoses, namely prostate, hematological malignancies, colorectal, lung, and other cancers. Oncologists should be aware that one-third of male patients modify their diet and/or search for spiritual guidance, particularly when diagnosed with metastatic cancer.

Phase II study of IV vinflunine in patients with chemotherapy naive metastatic malignant melanoma.

This phase II study evaluated vinflunine in chemotherapy naive patients with metastatic melanoma. Vinflunine was administered at 350 mg/m(2) every 3 weeks, but after 9 patients this was reduced to 320 mg/m(2) based on interim analyses of all phase II trials. A partial response was observed in 1 of the first 9 patients (11.1%) treated at 350 mg/m(2), which gives a 3.0% [95% confidence interval (CI): 0.08-15.8] response rate in 33 patients. No change was the best response in 13 patients (39.4%) with progressive disease in 16 (48.5%) and 3 were not evaluable for response. The time to response was 1.4 months and duration was 6 months. At 350 mg/m(2) grade 4 neutropaenia occurred in 3 patients (33.3%) and grade 3 in 2 patients (22.2%) while at 320 mg/m(2) grade 4 neutropaenia occurred in 6 patients (25%) and grade 3 in 3 patients (12.5%) with 2 episodes of grade 3 febrile neutropaenia. Two patients (8.3%) had grade 3 anaemia. These results do not show activity at this dose and schedule for vinflunine in patients with chemotherapy naive metastatic melanoma.

Why we will need to learn new skills to control cancer.

As a society and as specialists involved in the diagnosis and management of cancer, we must begin to find new cost-effective ways to provide equitable access to the innovative, effective and expensive drugs that may begin to make cancer a chronic rather than rapidly lethal disease. Drugs such as trastuzumab and gefitinib are safer 'targeted therapies' that only attract government subsidies after the pathologist identifies the target present in a minor subset of patients. Nonetheless, funding for pathological identification of these targets remains a challenge. To illustrate, gefitinib may produce 'Lazarus' responses and prolonged survival among patients with epidermal growth factor receptor mutation-positive non-small-cell lung cancer. Many such examples will enter the clinical domain in the coming years. As we enter this era of personalized medicine, we argue that the use of expensive targeted therapies should be limited to pathologically proven indications because truly effective drugs are best applied to those individuals who would most benefit. It follows that medical oncologists should be trained properly to use targeted therapies. Then a new generation of oncologists would be empowered to participate in the iterative cycles of research between bench and bedside that are necessary for optimal use of biotherapies and their integration into multimodality cancer treatment programmes. We propose that cancer pathology be made available as a training option in the postgraduate education of medical oncologists. Oncologists and pathologists may jointly administer and mutually accredit the training module, which may also contribute towards the award of a higher degree.

Pharmacokinetics of trimetrexate administered by five-day continuous infusion to patients with advanced cancer.

The disposition of the methotrexate analogue trimetrexate (TMTX, NSC 352122; 2,4-diammino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]qui nazoline) was determined in a Phase I study in 16 patients with refractory or relapsing cancer. The drug was administered by continuous 5-day infusion at doses of 5 to 60 mg/m2/120 h (1-12 mg/m2 daily for 5 days). Plasma and urine collections were made during and after infusion and TMTX levels were quantitated by a specific and sensitive high-performance liquid chromatographic assay. Estimates of pharmacokinetic parameters were similar when determined by either compartmental or noncompartmental methods. There were no significant differences in parameters between the first and second courses of treatment to 10 of the patients. Significant linear relations between TMTX dose and the area under curve of plasma TMTX (r2 = 0.858, P = 0.0001) and the steady-state TMTX plasma level (r2 = 0.764, P = 0.0001) were established. Total TMTX clearance was 30.4 +/- 7.6 (SD) ml/min/m2, renal clearance 7.80 +/- 3.9 ml/min/m2, nonrenal clearance 23.2 +/- 7.1 ml/min/m2, volume of distribution 32.8 +/- 16.6 liters/m2, and terminal half-life 13.4 +/- 7.0 h. The percentage of the trimetrexate dose excreted unchanged in urine ranged from 8.4 to 40.7% (mean, 24.9 +/- 9.2%) and was related to creatinine clearance (r2 = 0.312, P = 0.010). Trimetrexate renal clearance was also related to urine flow (r2 = 0.330, P = 0.008). Trimetrexate pharmacokinetics was linear over the dose range 5 to 60 mg/m2 when given by 5-day continuous infusion to patients but there was evidence of urine flow-dependent renal clearance which requires further examination.

A prospective study of topical dimethyl sulfoxide for treating anthracycline extravasation.

Twenty patients with extravasation of anthracyclines were treated on a single-arm pilot study with topical 99% dimethyl sulfoxide (DMSO) and observed for 3 months with regular examinations and photographs. DMSO was applied to approximately twice the area affected by the extravasation and allowed to air dry. This was repeated every six hours for 14 days. The initial signs of extravasation included swelling in 17 patients, erythema in 15, and pain in 12. The median area of damage was 8.25 cm2 and a median of 25 minutes elapsed between extravasation and application of DMSO with one patient not treated until seven days postextravasation. Sixteen patients were observed for 3 months, two died of disease earlier after receiving 2 weeks of DMSO and three days of DMSO, respectively, and two were lost to follow-up having received one day and five days of DMSO. In no patient did extravasation progress to ulceration or require surgical intervention, suggesting with 95% confidence a true ulceration rate of between 1% and 17%. At 3 months there was no sign of residual damage in six patients, while a pigmented indurated area remained in ten. Two patients had a recall reaction with increased pain at the extravasation site when further intravenous (IV) doxorubicin was administered. The only toxicities of DMSO included a burning feeling on application subsequently associated with itch, erythema, and mild scaling. Blisters occurred in four patients. Six patients reported a characteristic breath odor associated with DMSO. Topical DMSO appears to be a safe and effective treatment for anthracycline extravasation.

Phase II trial of a 3-hour infusion of paclitaxel in previously untreated patients with advanced non-small-cell lung cancer.

PURPOSE: To determine the antitumor activity and toxicity of paclitaxel administered as a 3-hour infusion in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-one patients with advanced measurable or assessable NSCLC and performance status 0 to 2 who had not received prior chemotherapy were treated with paclitaxel 175 mg/m2 over 3 hours with premedication. Cycles were repeated every 3 weeks for a maximum of nine cycles. Most patients had prior radiotherapy (57%), extrathoracic metastatic disease (65%), and measurable disease (75%). Twenty-two percent had previously untreated stage III disease. RESULTS: The objective response rate was five of 51 (10%; 95% confidence interval, 3% to 21%). No subgroup with a higher response rate could be identified. There were no complete responses (CRs) and all responses lasted less than 5 months. Treatment was well tolerated with brief World Health Organization (WHO) grade IV neutropenia in only 16% of patients. Grade III/IV myalgia/athralgia occurred in 22% of patients. No significant hypersensitivity reactions occurred. CONCLUSION: The antitumor activity of this dose and schedule appears inferior to that reported in previously published phase II trials in NSCLC that used higher doses of paclitaxel infused over 24 hours, although confidence intervals for response overlap. Determining the optimal dose and schedule for using paclitaxel in NSCLC requires further investigation, and these results should caution against using shorter infusions outside appropriate clinical trials.

Carboplatin (CBDCA, JM-8) and VP-16-213 in previously untreated patients with small-cell lung cancer.

The efficacy and toxicity of carboplatin 100 mg/m2, administered intravenously (IV) daily X 3, and VP-16-213 120 mg/m2, IV daily X 3, administered every 28 days for six courses, was assessed in 94 (36 limited stage, 58 extensive stage) previously untreated patients with small-cell lung cancer. Mediastinal irradiation using 50 Gy in 25 fractions was given to all limited-stage patients with a complete (CR) or partial response (PR) after three chemotherapy courses. Cranial irradiation was administered to all patients with CR. Objective responses were seen in 77% (CR 40%, PR 37%) of patients with limited-stage and 58% (CR, 9%; PR, 49%) with extensive-stage disease. Median relapse-free survival for objective responders with limited stage was 14.6 months and 7.9 months for extensive-stage patients. Median relapse-free survival following CR was 15.4 months and 8.5 months for PR. Median survival was 15.3 months for limited-stage and 8.1 months for extensive-stage patients. The combination was well tolerated with mild nausea or less (World Health Organization [WHO] grade 0 or 1) in 62% of patients and minimal mucositis, renal, neurotoxicity, or ototoxicity. Neutropenia less than 1.0 X 10(9)/L (WHO grade 3 or 4) was seen in 63% of patients, with two deaths from infection while neutropenic. The combination of carboplatin and VP-16-213 is a new, active program with low toxicity when applied intensively in previously untreated patients with small-cell lung cancer.

Lorazepam: a randomized, double-blind, crossover study of a new antiemetic in patients receiving cytotoxic chemotherapy and prochlorperazine.

Lorazepam was compared to placebo to assess its control of nausea and vomiting in patients receiving cytotoxic chemotherapy and prochlorperazine. The study design was a randomized, double-blind crossover in which three consecutive chemotherapy courses were compared so that each patient acted as his or her own control. Of 107 patients entered, 80 were evaluable for analysis. Lorazepam significantly reduced the severity and duration of nausea, the severity of vomiting, and the number of vomiting episodes when compared to placebo. Anxiety was reduced during lorazepam courses but not significantly when compared to placebo. There was significantly more sedation with lorazepam courses. Overall, patients preferred lorazepam courses although this preference was significant only in the patient subset receiving doxorubicin and cyclophosphamide. Lorazepam is a useful adjunct to prochlorperazine in patients receiving cytotoxic chemotherapy.

Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer.

PURPOSE: To determine the place of single-agent paclitaxel compared with nonanthracycline combination chemotherapy as front-line therapy in metastatic breast cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic breast cancer were randomized to receive either paclitaxel 200 mg/m(2) intravenously (IV) over 3 hours for eight cycles (24 weeks) or standard cyclophosphamide 100 mg/m(2)/d orally on days 1 to 14, methotrexate 40 mg/m(2) IV on days 1 and 8, fluorouracil 600 mg/m(2) IV on days 1 and 8, and prednisone 40 mg/m(2)/d orally on days 1 to 14 (CMFP) for six cycles (24 weeks) with epirubicin recommended as second-line therapy. RESULTS: A total of 209 eligible patients were randomized with a median survival duration of 17.3 months for paclitaxel and 13.9 months for CMFP. Multivariate analysis showed that patients who received paclitaxel survived significantly longer than those who received CMFP (P =.025). Paclitaxel produced significantly less severe leukopenia, thrombocytopenia, mucositis, documented infections (all P <.001), nausea or vomiting (P =.003), and fever without documented infection (P =.007), and less hospitalization for febrile neutropenia than did CMFP (P =.001). Alopecia, peripheral neuropathy, and myalgia or arthralgia were more severe with paclitaxel (all P <.0001). Overall, quality of life was similar for both treatments (P > = .07). CONCLUSION: Initial paclitaxel was associated with significantly less myelosuppression and fewer infections, with longer survival and similar quality of life and control of metastatic breast cancer compared with CMFP.

Phase I trial of cremophor EL with bolus doxorubicin.

Cremophor EL (cremophor), a component of the paclitaxel formulation, can potentially reverse P-glycoprotein-associated multidrug resistance. A Phase I trial of cremophor as a 6-h infusion every 3 weeks was performed with bolus doxorubicin (50 mg/m2). The cremophor dose was escalated from 1 to 60 ml/m2. A standard paclitaxel premedication was given before cremophor. Using a bioassay, potentially active cremophor levels (> or = 1 microl/ml) were measured in plasma from patients receiving cremophor doses of 30, 45, and 60 ml/m2. A cross-over design was used to assess the influence of cremophor 30 ml/m2 on the pharmacokinetics of doxorubicin and doxorubicinol. The plasma area under the concentration versus time curve (AUC) of doxorubicin increased from 1448 +/- 350 to 1786 +/- 264 ng/ml x h (P = 0.02) in the presence of cremophor, whereas the AUC of doxorubicinol increased from 252 +/- 104 to 486 +/- 107 ng/ml x h (P = 0.02). This pharmacokinetic interaction was associated with significantly increased neutropenia. With reduction of the doxorubicin dose to 35 mg/m2, the cremophor dose was increased to 60 ml/m2. Dose-limiting toxicities occurred in two of six patients after 45 ml/m2 and two of four patients after 60 ml/m2, which included febrile neutropenia and grade III cremophor-related toxicities of rash, pruritus, headache, and hypotension. All patients who received 45 ml/m2 cremophor reached plasma levels > or = 1.5 microl/ml, but at 60 ml/m2, only two of four reached this level, and the calculated plasma clearance of cremophor was significantly faster at this dose. One patient with hepatoma resistant to epirubicin achieved a near-complete response. Cremophor 45 ml/m2 over 6 h with 35 mg/m2 doxorubicin is recommended for further studies. The pharmacokinetic interaction between cremophor and doxorubicin is quantitatively similar to that described in trials of paclitaxel with doxorubicin and suggests that the cremophor in the paclitaxel formulation is responsible.

Treatment and survival from colorectal cancer: the experience of patients at South Australian teaching hospitals between 1980 and 2002.

AIMS: To evaluate trends in colorectal cancer survival and treatment at South Australian teaching hospitals and degree of adherence to treatment guidelines which recommend adjuvant chemotherapy for Dukes' C colon cancers and combined chemotherapy and radiotherapy for high-risk rectal cancers. MATERIALS AND METHODS: Trends in disease specific survival and primary treatment were analysed, and comparisons drawn between diagnostic epochs, using cancer registry data from South Australian teaching hospitals. Statistical methods included univariate and multivariable disease specific survival analyses. RESULTS: Five-year survival increased from 48% in 1980-1986 to 56% in 1995-2002. Largest gains were for stage C, where survivals were higher when chemotherapy was part of the primary treatment. By comparison, gains in 1-year survival were largest for stage D. Chemotherapy was provided for 4% of patients with colorectal cancers in 1980-1986, increasing to 32% in 1995-2002. Among stage C cases below 70 years at diagnosis, the proportion having chemotherapy increased to 83% in 1995-2002. The most common chemotherapy was fluorouracil (5FU) as a single agent in 1980-1986 and 5FU with leucovorin in 1995-2002. As expected, radiotherapy was used more frequently for rectal than colon cancers, and particularly for stage C. Among stage C rectal cases below 70 years, the proportion having radiotherapy increased from 10% in 1980-1986 to 57% in 1995-2002. Approximately 93% of colorectal cancers were treated surgically. Patients not treated surgically tended to be aged 80 years or more and to present with distant metastases. CONCLUSIONS: Trends in chemotherapy and radiotherapy accord with evidence-based recommendations. There have been reassuring gains in survivals after adjusting for stage, grade and other prognostic indicators. The data show survival gains and treatment patterns that individual hospitals can use as benchmarks when evaluating their own experience.

The roles of patient and observer assessments in anti-emetic trials.

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.

Concurrent radiotherapy and continuous ambulatory infusion 5-fluorouracil in advanced head and neck cancer.

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.

Prognostic value of quality of life scores in a trial of chemotherapy with or without interferon in patients with metastatic malignant melanoma.

In a multi-centre randomised clinical trial comparing dacarbazine (DTIC) plus recombinant interferon-alfa2a (IFN) versus DTIC alone for patients with metastatic malignant melanoma, aspects of quality of life (QL) were measured prospectively by patients using linear analogue self assessment (LASA) scales including the GLQ-8 and by doctors using Spitzer's QL Index. QL scores and performance status at the time of randomisation were available for 152 of 170 eligible patients. These scores carried significant prognostic information. In univariate analyses, Spitzer QL Index assessed by the doctor and LASA scores for physical wellbeing (PWB), mood, pain, appetite, nausea and vomiting, GLQ-8 total and overall QL were significant (P < 0.01) predictors of subsequent survival. QL Index and LASA scales for mood, appetite, and overall QL remained independently significant (all P < 0.05) in multivariate models allowing for significant prognostic factors other than QL (liver metastases and performance status). These findings closely parallel those in patients with metastatic breast cancer. They add further validity to the QL Index and LASA scores, provide the first evidence of the prognostic significance of the GLQ-8, and argue strongly for the routine assessment of QL in future therapy trials.

A randomised double blind crossover study of domperidone and prochlorperazine suppositories for controlling emesis in outpatients receiving chemotherapy.

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 effect of danazol on tumour control and weight loss in patients on tamoxifen therapy for advanced breast cancer: a randomised double-blind placebo controlled trial.

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.

A randomised double-blind study of high-dose intravenous prochlorperazine versus high-dose metoclopramide as antiemetics for cancer 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.

Phase II study of paclitaxel and oral etoposide in patients with locally advanced or metastatic non-small cell lung cancer.

The combination of paclitaxel and etoposide was evaluated in a phase II study in patients with locally advanced or metastatic non small-cell lung cancer (NSCLC). Thirty-five patients, median age 61, received treatment with paclitaxel 200 mg/m (2) intravenous over 3 h on day 1, and oral etoposide, 100 mg daily on days 1-5. Cycles were repeated every 21 days for a maximum of nine cycles, or until progression occurred. Twenty-eight patients had stage IV disease, and seven patients had stage IIIA or B disease. There was one complete and seven partial responses (overall response rate, 23%). Two of these responses were in patients with stage III disease (29%) and six in patients with stage IV disease (21%). Median survival was 8.7 months, and 36% of patients were alive at 1 year. There were no treatment-related deaths and little grade 3 or 4 non-haematological toxicity although grade 3 or 4 neutropenia occurred in 60% of patients (33% of cycles). There were four episodes of febrile neutropenia. The combination of paclitaxel and oral etoposide is active in advanced NSCLC and can be delivered with acceptable toxicity.