Comparison of two standard chemotherapy regimens for good-prognosis germ-cell tumours: a randomised trial. Australian and New Zealand Germ Cell Trial Group.

BACKGROUND: Most patients with metastatic germ-cell tumours are cured with chemotherapy. However, the optimum chemotherapy regimen is uncertain, and there is variation in international practice. We did a multicentre randomised trial to compare two standard chemotherapy regimens for men with good-prognosis germ-cell tumours. METHODS: Good prognosis was defined by modified Memorial Sloan-Kettering criteria. The first regimen (regimen A) was based on treatment recommendations from Indiana University and comprised three cycles of 20 mg/m2 cisplatin on days 1-5, 100 mg/m2 etoposide on days 1-5, and 30 kU bleomycin on days 1, 8, and 15, repeated every 21 days. The second regimen (regimen B) was based on the control regimen of a published randomised clinical trial and comprised four cycles of 100 mg/m2 cisplatin on day 1, 120 mg/m2 etoposide on days 1-3, and 30 kU bleomycin on day 1, repeated every 21 days. The primary outcome measure was overall survival. Analysis was by intention to treat. FINDINGS: 166 patients were randomised, 83 to each regimen. The trial was stopped when the second planned interim analysis met predefined stopping rules. The median follow-up was 33 months. Overall survival was substantially better with regimen A (three vs 13 deaths, hazard ratio 0.22 [95% CI 0.06-0.77], p=0.008). This difference was due to deaths from cancer (one vs nine), and not deaths from treatment (two vs two) and remained significant after adjustment for other prognostic factors (0.25 [0.07-0.88], p=0.03). INTERPRETATION: In men with good-prognosis germ-cell tumours, the regimen developed at Indiana University is superior to the alternative regimen studied in this trial. The lower total dose and dose-intensity of bleomycin and the lower dose-intensity of etoposide in regimen B could be responsible for the worse outcome.

Phase II study of thalidomide in the treatment of recurrent glioblastoma multiforme.

Treatment options and prognosis remains poor for patients with recurrent glioblastoma multiforme. These tumors are highly vascularised and over express angiogenic factors such as vascular endothelial growth factor and may potentially be responsive to antiangiogenic therapies. We present the results of a phase II trial of Thalidomide, an antiangiogenic agent, in the treatment of recurrent glioblastoma multiforme. Patients were treated with 100 mg/day of Thalidomide, increased at weekly intervals by 100 mg to a maximum tolerated dose of 500 mg/d. Forty-two patients were enrolled, with 38 patients being assessable for response and 39 for toxicity. Two patients (5%) achieved a partial response and 16 (42%) had stable disease. The median survival was 31 weeks and the 1-year survival was 35%. Patients who had a partial response or stable disease had either a stabilisation or improvement in quality of life scores or performance status. Overall Thalidomide was well tolerated with no grade 4 toxicities and no treatment related deaths. The median maximum tolerated dose was 300 mg/day. The most common toxicity was fatigue to which patients developed tachyphylaxis. There was no correlation demonstrated with plasma vascular endothelial growth factor levels and response or survival. Thalidomide is a well-tolerated drug that may have some activity in the treatment of recurrent glioblastoma. Optimum dosing with antiangiogenic agents is currently under investigation. Chronic low dose therapy may be required to see conventional responses or improvements in time to progression. The dose required to achieve optimal biological impact may be better defined once we have established reliable surrogate endpoints.

The predictive value of body protein for chemotherapy-induced toxicity.

BACKGROUND: The use of body surface area in determining chemotherapy dosing, particularly in the obese, remains controversial. Total body nitrogen (TBN) measurement in patients with serious illness has been suggested to be an accurate predictor of clinical course. The ability of TBN to predict chemotherapy-induced neutropenia was examined in the current study. METHODS: TBN measurements were performed in 31 female outpatients with breast carcinoma who were undergoing standard cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based chemotherapy (median age, 48 years; range, 26- 77 years). TBN was measured using the in vivo neutron capture analysis technique on Day 1 of Cycles 2-6. The chemotherapy toxicity index used was the absolute neutrophil count nadir (ANCN). Neutropenia was defined as an ANCN < 1.0 x 10(9)/L. The nitrogen index (NI) (TBN expressed as a percentage of age-, gender-. and height-matched healthy patients) then was compared with the corresponding ANCN values. RESULTS: Using receiver operating characteristics analysis, a "cut-off" value of NI = 0.89 was found. In this group of patients, when the NI was < 0.89, 11 of 13 courses in 7 patients (85%) led to an ANCN of < 1.0 x 10(9)/L, and when the NI was > 0.89, 29 of 109 courses (27%) led to an ANCN of < 1.0 x 10(9)/L (P < 0.0001). CONCLUSIONS: In this small group of breast carcinoma patients, the NI was found to be the most powerful predictor of neutropenia after CMF-based chemotherapy. The authors conclude that NI may be a useful clinical tool in identifying patients at a higher risk of chemotherapy-induced toxicity when widely distributed drug combinations such as CMF are used, and warrants further study with other commonly used drugs or drug regimens.

Changes in body composition during breast cancer chemotherapy with the CMF-regimen.

Weight gain is a reported problem associated with adjuvant chemotherapy for breast cancer and often generates psychosocial stress in women [1]. It also may affect prognosis and survival. Changes in body composition and weight during chemotherapy, particularly adjuvant treatment of breast carcinoma, have been previously reported [1-3]. Multiple reasons for this weight gain have been suggested though few theories have been scientifically validated [4]. The aim of this study was to investigate body composition and its relationship to weight change associated with the CMF-based breast cancer chemotherapy protocols. Total body nitrogen (TBN), body fat, total body water (TBW), and anthropometric measurements were conducted on 25 female out-patients (median age 47, range 26-70 years) receiving adjuvant CMF-based chemotherapy for breast cancer. Total body nitrogen was measured using the In Vivo Neutron Capture Analysis (IVNCA) technique (on day 1 of cycles 2-6) and TBP was calculated by multiplying TBN by 6.25 [5]. Nitrogen Index (NI) was calculated by expressing TBN as a percentage of normal. There was a significant increase in mean body weight during chemotherapy of 2.35 kg (p < 0.0001). Serial measurements showed no significant change in mean TBN, NI, or percentage body fat. Break down of body weight showed a significant increase in mean TBW of 0.79 kg (p = 0.003) and mean fat mass of 1.49 kg (p = 0.008). We conclude that weight gain observed during adjuvant chemotherapy for breast carcinoma is primarily due to an increase in fat and TBW.

Management of germ cell carcinoma: state of the art.

The management of all stages of germ cell carcinomas is fairly well defined with generally high rates of cure. In stage I disease surveillance and chemotherapy on relapse is as successful as initial adjuvant chemotherapy. More than 95% of patients will survive. In stage II disease either three to four cycles of chemotherapy, or retroperitoneal node dissection and subsequent chemotherapy if more than six nodes are positive or nodes are > 2 cm diameter, or there is extra nodal extension, are equivalent with survival > 95%. For stage III disease, a new international prognostic classification has determined that the level of tumour markers, presence of non pulmonary visceral disease, or a mediastinal primary, indicate a poorer prognosis. Long term follow up studies reveal an overall percentage of relapses (4-5%) beyond two years and the need for long term follow up.

Fatal pulmonary toxicity resulting from treatment with gemcitabine.

BACKGROUND: Pulmonary toxicity reported with gemcitabine is usually mild and self-limiting. The authors report a series of three patients who had life-threatening pulmonary toxicity after receiving gemcitabine. METHODS: The three patients presented to two major teaching hospitals with significant pulmonary dysfunction while receiving gemcitabine. Case data were obtained from patient records. A review of the literature was done to seek reports of pulmonary toxicity with gemcitabine and cytosine arabinoside (ara-C). RESULTS: The common features of the respiratory illnesses of the three patients in this study were tachypnea, marked hypoxemia, and an interstitial infiltrate on chest radiograph consistent with pulmonary edema. There was no evidence of underlying heart disease in any patient. In addition, there was no evidence of infection, metabolic causes, or lymphangitic carcinomatosis to explain the clinical findings. Two patients died, and postmortem examination confirmed acute RDS (respiratory distress syndrome), whereas in the third patient a transbronchial biopsy showed interstitial pneumonitis. These findings were consistent with drug-induced pulmonary toxicity. Diuretics and corticosteroids were useful measures for treating the patients' symptoms, and one patient survived after gemcitabine was withdrawn. CONCLUSIONS: These three cases of acute RDS may be the result of a capillary leak phenomenon due to treatment with gemcitabine, as observed in patients given intermediate dose and high dose ara-C, a drug similar in structure and metabolism to gemcitabine. The authors suggest caution in repeated administration of gemcitabine to patients who develop unexplained noncardiogenic pulmonary edema. Withdrawing gemcitabine and administering corticosteroids and diuretics may help to avert a fatal outcome.

Australian multicentre phase II trial of paclitaxel in women with metastatic breast cancer and prior chemotherapy.

OBJECTIVE: To determine the efficacy and safety of paclitaxel given as a three-hour infusion in patients with metastatic breast cancer which had progressed despite hormonal therapy and/or chemotherapy. DESIGN AND SETTING: Multicentre phase it trial undertaken in five major centres or hospitals in Sydney, Melbourne and Adelaide. PATIENTS AND METHODS: 50 patients with clinically or radiologically measurable or evaluable metastatic breast cancer recruited between March and July 1993. All had received prior chemotherapy, with subsequent disease progression. INTERVENTION: Paclitaxel (Anzatax, Faulding) was given at a dose of 175 mg/m2 intravenously over three hours every three weeks for up to nine courses. MAIN OUTCOME MEASURES: Response rate (partial or complete); duration of progression-free survival; duration of survival; and adverse reactions. RESULTS: Patients had a median age of 51 years; 62% had received at least two prior drug regimens for metastatic breast cancer and 48% had anthracycline-resistant tumours. A median of six paclitaxel courses was given per patient. Overall response rate was 18% (95% confidence interval [95% CI], 9%-31%), with complete responses in four patients (8%). In patients with anthracycline-resistant tumours, response rate was 25% (95% CI, 10%-47%). Response was not influenced by extent of prior treatment. Estimated median progression-free survival was 4.1 months (95% CI, 3.2-6.0 months) and estimated median survival was 6.3 months (95% CI, 6.2-10.3 months). Treatment was well tolerated, with neutropenia the major toxic effect. CONCLUSIONS: Paclitaxel (three-hour infusion) has significant activity in heavily pretreated patients with metastatic breast cancer, including anthracycline-resistant tumours.

Long-term follow-up of a randomised trial of combined chemoradiotherapy induction treatment, with and without maintenance chemotherapy in patients with small cell carcinoma of the lung.

The toxicity and efficacy of concomitant chemotherapy and radiotherapy as induction therapy was evaluated in patients with previously untreated small cell carcinoma of the lung (SCLC), and in responding patients the value of maintenance chemotherapy was examined. 202 patients received induction chemotherapy with cisplatin and etoposide (EP), in combination with cranial and local radiotherapy. 85 patients (42%) developed grades III and IV myelosuppression, the main toxicity of induction treatment. Of the 154 responding patients, 129 were randomised to maintenance chemotherapy with vincristine, doxorubicin and cyclophosphamide (VAC) or no further treatment. The response rate for the limited disease patients (LD) was 87%, 62% achieving a complete response (CR) and the response rate for extensive disease patients (ED) was 68%, with 26% achieving a CR. 17 patients (11%) completed 10 courses of maintenance chemotherapy. 32 patients (57%) developed grade III and IV neutropenia. Median survival for all patients was 53 weeks (LD, 70 weeks; ED, 42.5 weeks). There was no significant difference in overall survival (OS) or disease-free survival (DFS) in the two randomisation arms. This study shows that EP combined with radiotherapy is an effective induction regimen in SCLC. Maintenance chemotherapy with VAC is not associated with increased survival but has significant toxicity after such induction treatment.

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.

Phase II study of high dose epirubicin in combination with cyclophosphamide in patients with advanced breast cancer.

BACKGROUND: Combination chemotherapy for metastatic breast cancer will palliate symptoms in the majority of patients but only a small percentage will have prolonged survival. Higher doses of doxorubicin lead to increased response rates in breast cancer and early studies have shown that epirubicin could be tolerated in higher doses with less relative toxicity than doxorubicin. AIMS: This study was initiated to assess the dose of epirubicin that could be tolerated by escalating its dose while maintaining a fixed dose of cyclophosphamide. Simultaneously tumour response rate, spectrum of toxicities, duration of response and overall survival in patients with metastatic breast cancer were assessed. METHODS: Patients with metastatic breast cancer commenced chemotherapy with a starting dose of epirubicin of 120 milligram per metre squared (mg/m2) and cyclophosphamide 600 mg/m2. The dose of epirubicin was to be escalated or reduced depending on toxicity. RESULTS: Forty female patients were entered into this study and three patients withdrew because of toxicity. Overall tumour response rate was 75% with 27.5% of patients obtaining a complete response. Median time to progressive disease was 35 weeks and median overall survival was 48 weeks, with median survival for complete responders being 103 weeks. Thirty-one (77%) patients completed five or more courses of treatment. Haematological toxicity was the main side effect and 70% of patients required a dose reduction. No patients were eligible for a dose escalation. One patient died as a consequence of neutropenic sepsis. Four (10%) patients had treatment ceased because of decrease in left ventricular ejection fraction and one patient died as a consequence of heart failure. Four patients remain alive. CONCLUSIONS: High dose epirubicin combined with cyclophosphamide is an effective treatment regimen for metastatic breast cancer obtaining higher overall response rates with increased percentage complete responses compared to conventional dose chemotherapy. Although toxicity was increased, high dose chemotherapy was well tolerated and mortality associated with treatment was not increased. No dose escalations of epirubicin were possible and a dose of 90 mg/m2 of epirubicin would be the maximum dose when used in combination with cyclophosphamide. Further trials are required to determine the influence of this high dose therapy on survival duration and whether comparable benefits can be achieved with shorter durations of therapy.

Bone presentation of non-Hodgkin's lymphoma: experience at the Royal North Shore Hospital, Sydney; highlighting primary bone lymphoma.

BACKGROUND: Primary lymphoma of bone (PLB) is a rare form of extranodal lymphoma. Between 1975 and 1992 39 patients with lymphoma presenting in bone were seen at the Royal North Shore Hospital (RNSH), Sydney. Of these, 12 (31%) had truly localised disease (Stage IE). AIMS: Patients were studied retrospectively to determine the prognostic significance of bony involvement per se versus involvement of a single bony site, and to determine the impact of treatment modality on outcome. METHODS: The 39 patients were divided into three groups according to extent of disease; single osseous site (Stage IE), multifocal bone, and bone plus visceral and/or nodal disease. Kaplan-Meier survival curves were constructed, and five year actuarial survival stated. Cox regression analysis was used to determine hazard ratios. Overall survival was used as the end-point. RESULTS: A trend for better survival was noted with Stage IE disease. Multifocal and disseminated disease appeared to have a poorer outcome when assessed by hazard ratio, with a value of 3 (95% CI 0.87-10.4; p = 0.08), compared to unifocal disease. Radiotherapy alone was as effective as combined modality treatment although patient numbers were too small for statistical confirmation. CONCLUSIONS: The stage of lymphoma, rather than bony involvement per se, seems to have more prognostic importance. Radiotherapy alone offered equivalent results to combined modality treatment in this series.

The importance of bleomycin in combination chemotherapy for good-prognosis germ cell carcinoma. Australasian Germ Cell Trial Group.

PURPOSE: In an effort to maintain the excellent long-term results achieved with combination chemotherapy for good-prognosis germ cell carcinoma, but to reduce the toxicities encountered, a randomized trial was conducted comparing cisplatin and vinblastine with or without bleomycin. PATIENTS AND METHODS: Two hundred eighteen assessable patients with a good prognosis were randomized to receive induction chemotherapy with cisplatin 100 mg/m2 intravenously (IV) day 1 and vinblastine 6 mg/m2 IV days 1 and 2 every 3 weeks (PV) with or without bleomycin 30 mg intramuscularly (IM) weekly (PVB) for a maximum of 12 weeks. Once maximum response was achieved, patients with a complete remission (CR) received two courses of consolidation chemotherapy, while those with residual abnormalities and normal tumor markers underwent surgical resection whenever possible. RESULTS: Toxicities encountered in this study were clearly greater for those patients who received bleomycin, with significantly more leukopenia, thrombocytopenia, anemia, alopecia, and renal and pulmonary toxicities. The proportion of patients who achieved CR and had no evidence of disease (resection of all viable malignancy) was 89% for PV and 94% for PVB (P = .29). After a minimum of 4 years of follow-up, relapses have occurred in 7% of patients who received PV and 5% who received PVB. A total of five patients on each therapy arm were successfully treated with further salvage chemotherapy and surgery. Thus, deaths from progressive malignancy have occurred in 15% of patients on PV and 5% on PVB (P = .02), a rate that was partly offset by the higher proportion of toxic deaths with PVB (P = .06). CONCLUSION: Despite the toxicities encountered with bleomycin in cisplatin-based combination chemotherapy for these patients, complete deletion of this drug compromises therapeutic efficacy.

Continuous hepatic artery infusion of 5-fluorouracil for metastatic colorectal cancer localised to the liver.

Continuous regional delivery of chemotherapeutic agents offers the prospect of maximising dose intensity at the site of localised disease, while minimising systemic toxicity. This prospective phase II study evaluates the efficacy and toxicity of hepatic arterial infusion of 5-Fluorouracil (5-FU) via an implantable Infusaid pump in previously untreated patients with localised but unresectable hepatic metastases from colorectal cancer. In 25 patients the response rate was 56% and median survival was 15 months, comparable to previous reports utilising fluorodeoxyuridine (FUDR). Twenty per cent of patients (all responders) survived longer than three years. Systemic toxicity was trivial, and the practice of reducing the intensity of therapy when nausea or a rise in alkaline phosphatase occurred avoided the previously described local toxicity of biliary sclerosis seen frequently with FUDR. In selected patients, particularly those with more limited disease, this form of therapy is effective and well tolerated and warrants further evaluation as an alternative to FUDR.

Dual sequential non-cross-resistant chemotherapy for advanced stage squamous cell carcinoma of the cervix.

Forty-three patients with recurrent and metastatic squamous cell carcinoma of the cervix received a program of sequential combination chemotherapy incorporating induction with cisplatin, vinblastine, and bleomycin (PVB) and subsequent consolidation with 5-fluorouracil, doxorubicin, cyclophosphamide, and vincristine (FACV). The overall response rate was 62% and 10 patients (23%) achieved complete remission. Response status was improved in 11 patients at the completion of FACV after initial PVB therapy, including 9 complete remissions. The median survival for all patients in the study was 38 weeks and 50 weeks for the responding patients. Myelosuppression was the principal toxicity encountered and 10 episodes of neutropenic sepsis occurred, including one septic death. However, the only cumulative toxicity was peripheral neuropathy, although this was only moderate to severe in 2 patients. These results are encouraging, but will require confirmation in randomized comparison to cisplatin, presently accepted as standard single-agent therapy.

A phase II study of mitoxantrone in advanced gastric cancer.

Sixteen patients with advanced adenocarcinoma of the stomach were entered into a phase II study of mitoxantrone at a dosage of either 12 mg/m2 or 14 mg/m2 given at 3 weekly intervals. Nine patients had received prior chemotherapy including doxorubicin. No patients achieved either a complete or partial response, five patients had stable disease and the remainder disease progression. Moderate to severe leukopenia occurred in 10 patients with one septic death. Median survival for all patients was eight weeks (range 1-49 weeks). It is concluded that mitoxantrone has no worthwhile activity in gastric cancer at the described doses.

Current status of treatment for breast cancer.

Recent developments in the treatment of early stage breast cancer include mature data from randomised trials that indicate limited surgery with breast irradiation provide comparable survival to total or radical mastectomy. For patients undergoing radical mastectomy while post-operative radiotherapy should not be routine, when more than four axillary lymph nodes are involved at surgery or the primary tumour involves the medial quadrants, then local recurrence rates are significantly reduced by this radiotherapy. Overview statistical metanalyses of data from adjuvant therapy trials has confirmed that cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy reduced the risk of death by 24 +/- 6% compared to controls for premenopausal women. Whereas, administration of tamoxifen for more than one year to postmenopausal women with positive axillary lymph nodes and positive hormone receptor levels resulted in a 18 +/- 4% reduction in mortality. Similar adjuvant treatments in women with negative axillary lymph nodes but other adverse prognostic factors improves disease-free but not as yet overall survival. In advanced disease, the success of hormone manipulation is dependant on the presence and amount of oestrogen and progesterone receptor protein in either the primary breast tumour or a biopsied metastasis. If a response is achieved, this will be complete in 5-20% of patients with a median survival in excess of 18 months for responding patients and 25% remaining alive and disease-free beyond 30 months. Combination chemotherapy for patients with negative hormone receptors or aggressive disease achieve response in 50-60% of patients. Current activity to improve the therapeutic index of chemotherapy include less toxic analogs, priming hormones and high dose chemotherapy.

Effective salvage chemotherapy with etoposide, dactinomycin, and methotrexate in refractory germ cell cancer. Australasian Germ Cell Trial Group.

Fifty-one patients with advanced germ cell malignancy who had either failed to achieve complete remission with initial cisplatin, vinblastine, and bleomycin chemotherapy or who had relapsed after complete response (CR) to this therapy and then proven refractory on retreatment, were treated with etoposide (75 mg/m2 for 3 days), dactinomycin (1 mg/m2 day 1), and methotrexate (30 mg/m2 day 1) (EAM) every 3 weeks. Courses were continued until maximum response without empirical limit, and if complete remission was achieved, two courses of consolidation therapy were given before cessation of treatment. Thirteen patients (25%) were complete responders with residual masses containing fibrosis or benign teratoma being subsequently resected in seven patients. Two patients had persisting viable carcinoma within residual masses that were completely resected, leaving no evidence of disease (NED); the combined CR plus NED rate was 29%. The only pretreatment factor significantly influencing this response rate was tumor volume. Toxicities were moderate, with leukopenia being observed in 28% of patients, but it was severe in only 2%. There was one death from septicemia. Severe nausea and vomiting occurred in only 9% of patients and treatment-related stomatitis was observed in 42%. All patients achieving CR plus NED have been followed for a minimum of 5 years and no relapses have occurred, suggesting that these patients are cured. Unlike other regimens of salvage chemotherapy, this treatment program did not contain cisplatin and it is contended that a completely noncrossresistant drug regimen based on etoposide provides the opportunity to further improve the curability of patients with advanced germ cell cancer.

Dose intensity and outcome with combination chemotherapy for germ cell carcinoma. Australasian Germ Cell Trial Group.

Two hundred and fifty-three patients with advanced stage germ cell carcinoma received induction chemotherapy with vinblastine, bleomycin and cisplatin, sometimes with subsequent surgical resection of residual masses. Overall, 191 patients (76%) achieved complete remission or no evidence of disease after surgery (CR + NED). With 64 months median follow-up only 24 patients have relapsed (13%) and 68% of all patients treated are long-term survivors and 84% of patients entering CR + NED are alive. Toxicity with this chemotherapy was considerable, including seven deaths from leukopenia and septicaemia and eight deaths from bleomycin lung toxicity. Dose reductions or omissions of the drug from the treatment programme was necessary with cisplatin in 8% of patients, with vinblastine in 37% and with bleomycin in 35% of patients. Analysis of these alterations in dose intensity for each drug revealed that initial treatment response and subsequent survival were not compromised by reductions in intended doses of drug administered for either vinblastine or bleomycin. Too few patients had dose reductions of cisplatin for meaningful analysis. This apparent lack of major dose-response effect for either vinblastine or bleomycin in the present treatment programme for germ cell carcinoma has prompted the initiation of a randomized study to determine whether deletion of bleomycin from treatment for patients with good prognostic pretreatment characteristics improves the therapeutic index of this very successful therapy.

Double-blind randomized cross-over trial of dexamethasone and prochlorperazine as anti-emetics for cancer chemotherapy.

A double-blind randomized cross-over trial of dexamethasone and prochlorperazine as adjunctive anti-emetics with cancer chemotherapy was undertaken. The drugs were compared for cisplatin, doxorubicin and several other chemotherapy regimens. A total of 44 eligible patients were analysed. Assessment was made by questionnaire answered by the patient 24 h after the chemotherapy. The parameters compared were period of time for nausea and vomiting, number of vomiting episodes, degree of somnolence and insomnia and overall preference. In all cases there was no significant difference for either drug in its ability to suppress emetic effects. Neither drug gave adequate protection against cisplatin-containing regimens. We conclude that dexamethasone alone is equivalent to the more standard dopamine antagonists.