Subgroup analysis in RAISE: a randomized, double-blind phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab or placebo in patients with metastatic colorectal carcinoma progression.

BACKGROUND: The RAISE phase III clinical trial demonstrated that ramucirumab + FOLFIRI improved overall survival (OS) [hazard ratio (HR) = 0.844, P = 0.0219] and progression-free survival (PFS) (HR = 0.793, P < 0.0005) compared with placebo + FOLFIRI for second-line metastatic colorectal carcinoma (mCRC) patients previously treated with first-line bevacizumab, oxaliplatin, and a fluoropyrimidine. Since some patient or disease characteristics could be associated with differential efficacy or safety, prespecified subgroup analyses were undertaken. This report focuses on three of the most relevant ones: KRAS status (wild-type versus mutant), age (<65 versus ≥65 years), and time to progression (TTP) on first-line therapy (<6 versus ≥6 months). PATIENTS AND METHODS: OS and PFS were evaluated by the Kaplan-Meier analysis, with HR determined by the Cox proportional hazards model. Treatment-by-subgroup interaction was tested to determine whether treatment effect was consistent between subgroup pairs. RESULTS: Patients with both wild-type and mutant KRAS benefited from ramucirumab + FOLFIRI treatment over placebo + FOLFIRI (interaction P = 0.526); although numerically, wild-type KRAS patients benefited more (wild-type KRAS: median OS = 14.4 versus 11.9 months, HR = 0.82, P = 0.049; mutant KRAS: median OS = 12.7 versus 11.3 months, HR = 0.89, P = 0.263). Patients with both longer and shorter first-line TTP benefited from ramucirumab (interaction P = 0.9434), although TTP <6 months was associated with poorer OS (TTP ≥6 months: median OS = 14.3 versus 12.5 months, HR = 0.86, P = 0.061; TTP <6 months: median OS = 10.4 versus 8.0 months, HR = 0.86, P = 0.276). The subgroups of patients ≥65 versus <65 years also derived a similar ramucirumab survival benefit (interaction P = 0.9521) (≥65 years: median OS = 13.8 versus 11.7 months, HR = 0.85, P = 0.156; <65 years: median OS = 13.1 versus 11.9 months, HR = 0.86, P = 0.098). The safety profile of ramucirumab + FOLFIRI was similar across subgroups. CONCLUSIONS: These analyses revealed similar efficacy and safety among patient subgroups with differing KRAS mutation status, longer or shorter first-line TTP, and age. Ramucirumab is a beneficial addition to second-line FOLFIRI treatment for a wide range of patients with mCRC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01183780.

CA19-9 decrease at 8 weeks as a predictor of overall survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer.

BACKGROUND: A phase I/II study and subsequent phase III study (MPACT) reported significant correlations between CA19-9 decreases and prolonged overall survival (OS) with nab-paclitaxel plus gemcitabine (nab-P + Gem) treatment for metastatic pancreatic cancer (MPC). CA19-9 changes at week 8 and potential associations with efficacy were investigated as part of an exploratory analysis in the MPACT trial. PATIENTS AND METHODS: Untreated patients with MPC (N = 861) received nab-P + Gem or Gem alone. CA19-9 was evaluated at baseline and every 8 weeks. RESULTS: Patients with baseline and week-8 CA19-9 measurements were analyzed (nab-P + Gem: 252; Gem: 202). In an analysis pooling the treatments, patients with any CA19-9 decline (80%) versus those without (20%) had improved OS (median 11.1 versus 8.0 months; P = 0.005). In the nab-P + Gem arm, patients with (n = 206) versus without (n = 46) any CA19-9 decrease at week 8 had a confirmed overall response rate (ORR) of 40% versus 13%, and a median OS of 13.2 versus 8.3 months (P = 0.001), respectively. In the Gem-alone arm, patients with (n = 159) versus without (n = 43) CA19-9 decrease at week 8 had a confirmed ORR of 15% versus 5%, and a median OS of 9.4 versus 7.1 months (P = 0.404), respectively. In the nab-P + Gem and Gem-alone arms, by week 8, 16% (40/252) and 6% (13/202) of patients, respectively, had an unconfirmed radiologic response (median OS 13.7 and 14.7 months, respectively), and 79% and 84% of patients, respectively, had stable disease (SD) (median OS 11.1 and 9 months, respectively). Patients with SD and any CA19-9 decrease (158/199 and 133/170) had a median OS of 13.2 and 9.4 months, respectively. CONCLUSION: This analysis demonstrated that, in patients with MPC, any CA19-9 decrease at week 8 can be an early marker for chemotherapy efficacy, including in those patients with SD. CA19-9 decrease identified more patients with survival benefit than radiologic response by week 8.

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.

Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29.

INTRODUCTION: This randomised double-blind placebo-controlled study evaluated the addition of cediranib, an inhibitor of vascular endothelial growth factor receptors 1-3, to standard carboplatin/paclitaxel chemotherapy in advanced non-small cell lung cancer. METHODS: Eligible patients received paclitaxel (200mg/m(2)) and carboplatin (area under the concentration time curve 6) intravenously every 3 weeks. Daily oral cediranib/placebo 20mg was commenced day 1 of cycle 1 and continued as monotherapy after completion of 4-6 cycles of chemotherapy. The primary end-point of the study was overall survival (OS). The trial would continue to full accrual if an interim analysis (IA) for progression-free survival (PFS), performed after 170 events of progression or death in the first 260 randomised patients, revealed a hazard ratio (HR) for PFS of ⩽ 0.70. RESULTS: The trial was halted for futility at the IA (HR for PFS 0.89, 95% confidence interval [CI] 0.66-1.20, p = 0.45). A final analysis was performed on all 306 enrolled patients. The addition of cediranib increased response rate ([RR] 52% versus 34%, p = 0.001) but did not significantly improve PFS (HR 0.91, 95% CI 0.71-1.18, p = 0.49) or OS (HR 0.94, 95% CI 0.69-1.30, p=0.72). Cediranib patients had more grade 3 hypertension, diarrhoea and anorexia. CONCLUSIONS: The addition of cediranib 20mg daily to carboplatin/paclitaxel chemotherapy increased RR and toxicity, but not survival.

A multi-centre randomized, open-label phase II trial of continuous erlotinib plus gemcitabine or gemcitabine as first-line therapy in ECOG PS2 patients with advanced non-small cell lung cancer.

Erlotinib and gemcitabine are active in NSCLC and have synergy in other cancers. This study investigated the activity and tolerability of this combination as first-line therapy in ECOG PS 2 patients. Chemotherapy-naïve patients with NSCLC, either stage IIIB (with plural effusion) or stage IV, with measurable disease and ECOG PS 2, and adequate organ function were randomized to receive either erlotinib (150 mg/day p.o.) plus gemcitabine (1000 mg/m2, days 1, 8, 15, every 4 weeks) in Arm A or gemcitabine monotherapy (Arm B). The primary end-point was progression-free survival. Seventeen patients of a planned 120 patients were randomized (12 males; 16 Caucasians, 4 large cell, 9 adenocarcinoma; 13 former and 1 never smokers); 16 patients received treatment (8 in each arm). The incidence of treatment-related adverse events (AEs) was 8/8 in Arm A and 6/8 in Arm B; most AEs were grade 1 or 2. The most common treatment-related non-hematological AEs were grade 1 or 2 rash (7/8) and diarrhea (7/8) in Arm A. Two patients in Arm A had partial responses, with durations of 16 and 47 weeks, respectively. Overall disease control rate (N=15) was 86% in Arm A versus 50% for the control arm. Erlotinib plus gemcitabine for the treatment of ECOG 2 NSCLC patients warrants further investigation including intermittent erlotinib regimens.

Two different first-line 5-fluorouracil regimens with or without oxaliplatin in patients with metastatic colorectal cancer.

BACKGROUND: Oxaliplatin, 5-fluorouracil (5-FU), and leucovorin (LV) are standard first-line treatments for patients with metastatic colorectal cancer (mCRC). The aim of this multicentre, open-label, phase IIIb study was to assess the addition of oxaliplatin to two different 5-FU regimens. PATIENTS AND METHODS: Patients with previously untreated mCRC were randomised to arm A [two-weekly oxaliplatin 85 mg/m(2) + either continuous intravenous infusion (CIV) of 5-FU without LV or two-weekly bolus and CIV 5-FU + LV (LV5FU2)] or arm B (5-FU CIV or LV5FU2 alone). Irinotecan monotherapy was planned on progression. RESULTS: A total of 725 patients were enrolled. After a fixed follow-up of 2 years for each patient, 2-year survival rates were 27.3% and 24.8% in arms A and B, respectively (hazard ratio 0.93; 95% confidence interval 0.78-1.10). The addition of oxaliplatin significantly improved response rates (54.1 versus 29.8%; P < 0.0001) and median progression-free survival (7.9 versus 5.9 months; P < 0.0001). The most common grade 3-4 toxic effects were neutropenia (arm A, 33%; arm B, 5%), diarrhoea (arm A, 14%; arm B, 8%), and fatigue (arm A, 9%; arm B, 8%). CONCLUSIONS: Despite improved rates of tumour control, these results failed to demonstrate a survival benefit from the addition of oxaliplatin to infused 5-FU and lend further support to the use of sequential monotherapy in some patients with mCRC.

Concurrent end-phase boost high-dose radiation therapy for non-small-cell lung cancer with or without cisplatin chemotherapy.

The aim of this study was to audit the results of a high-dose, combined-modality prospective protocol for non-small-cell lung cancer in terms of survival, disease-specific survival and toxicity. One hundred and twenty-one patients with non-small-cell lung cancer were treated with a concurrent, end-phase, boost, high-dose radiotherapy protocol with 65 Gy in 35 fractions for more than 5 weeks. Sixty-six patients received radiotherapy alone (group 1), 29 received concurrent chemoradiation (group 2) and 26 received neoadjuvant and concurrent chemotherapy (group 3). Thirty-four patients had stage I disease, six had stage II and 81 had stage III. Overall median survival was 23 months: 75% at 1 year and 23% at 5 years. Median survivals for patients with stage I and stages II and III disease were 43 and 19 months, respectively. For stages II and III patients by groups 1-3, median survivals were 18, 25 and 18 months, respectively, and 2-year survivals were 36, 52 and 38%, respectively. Toxicity was acceptable. Overall, 9% had symptomatic pneumonitis and 7% had grades 3 and 4 oesophagitis. For those who had the mediastinum included in the volume, grade > or = 3 oesophagitis occurred in 0, 11 and 22% (n = 110, P = 0.001), respectively, for treatment groups 1-3. Overall treatment-related mortality was 3%, consisting of two septic deaths, one pneumonitis and possibly one late cardiac event, all occurring in patients who had chemotherapy (7% of 55 patients). Treatment-related mortality declined over the study period. Accelerated radiotherapy was well tolerated, with only moderate increased acute toxicity when combined with concurrent platinum chemotherapy. Toxicity was enhanced by induction chemotherapy. Overall survival outcomes were excellent for this condition. Continued use of this radiotherapy schedule is recommended as the platform for assessment of other chemotherapy schedules.

Radiologically placed temporary hepatic artery catheter for treatment of liver cancer.

Summary Hepatic artery infusion (HAI) chemotherapy is associated with higher response rates compared to systemic chemotherapy in those patients with unresectable liver malignancies. Operative hepatic artery catheter (HAC) insertion has significant morbidity and mortality, especially in patients with high-volume disease, some of whom may not respond to HAI chemotherapy. We report our experience in 45 patients with high-volume liver disease who were initially treated with HAI chemotherapy via a radiologically placed temporary HAC to try to select the responders who then went on to have an operative HAC. In these 45 patients who had 62 radiologically placed HAC, we found very few major complications, and certainly no complications such as cholecystitis, vascular or malperfusion problems.

Percutaneous radiofrequency ablation of pulmonary metastases in patients with colorectal cancer.

INTRODUCTION: This study aimed to assess the safety and efficacy of imaging-guided percutaneous radiofrequency ablation (RFA) for local control of lung metastases from colorectal cancer (CRC). METHODS: Twenty patients with lung metastases from CRC were treated with a RITA Starburst XL electrode and RITA 1500 generator using temperature control and impedance monitoring. Patients received intravenous sedation and analgesia, or local anaesthetic, and stayed in hospital for at least 24 h after treatment. RFA was assessed with computed tomography (CT) at 1 week and 1 month, and then every 3 months. RESULTS: Forty-four CRC lung metastases in 19 patients were treated successfully at 25 treatment sessions. Five of 19 patients were retreated for new lesions. There were 13 pneumothoraces following the 25 treatments, and six patients required drainage. The median length of follow-up was 730 (range 148-924) days. Six months after treatment CT demonstrated that three lesions had progressed, 25 metastases were stable or smaller, and 11 were no longer visible. At 12 months five metastases had progressed, 11 were smaller or stable, and nine were not visible. CONCLUSION: Percutaneous imaging-guided RFA was associated with modest morbidity. RFA can achieve local control of CRC lung metastases: nine of 25 metastases were not visible on CT at 12 months after treatment.

Gastroduodenal ulceration following hepatic arterial chemotherapy: the role of methylene blue endoscopy in the investigation of pain.

BACKGROUND: Unintended perfusion of the gastroduodenum may complicate hepatic arterial chemotherapy leading to mucosal ulceration. PATIENTS AND METHODS: In a review of 233 consecutive hepatic artery catheters placed, 61 patients were investigated for chemotherapy-related epigastric pain. Investigations included catheter imaging, upper gastrointestinal endoscopy with methylene blue injection via the hepatic artery catheter and angiography. RESULTS: Twenty patients (33%) demonstrated blue staining of the gastroduodenum. Angiography performed in 15 of these patients confirmed a misperfusing vessel in 13.The aberrant artery was successfully embolised and infusional chemotherapy recommenced in 11 patients. Forty-one patients had a negative dye test, of whom three had gastroduodenal ulcers, 14 had oesophagitis or gastroduodenitis, ten had catheter complications (leak n=2, arteritis n=5, pseudoaneurysm n=1, sepsis n=1), three had liver collections, five had floxuridine cholangitis and one had myocardial ischaemia. No cause could be found in 8 patients. No patient with a negative dye test developed unintended perfusion on repeat investigation.

Lipiodol avid liver metastases from adrenocortical carcinoma; prospects for therapy?

A young lady with liver metastases from adrenocortical carcinoma was given a tracer dose of lipiodol into the hepatic artery and her liver metastases were shown to be extremely lipiodol avid. A therapeutic dose of lipiodol I131 was then given. There was not, however, any evidence of response to this treatment.

The effect of celiac and renal artery outflows on near-wall velocities in the porcine iliac arteries.

The effects of the outflow of aortic blood through the celiac and renal arteries on the flow field in the external iliac arteries were studied under steady and physiologically realistic pulsatile flow conditions. Laser Doppler velocimetry (LDV) measurements were made close to the medial, lateral, ventral, and dorsal walls of the external iliac branches of a clear, flow-through replica of a porcine aorta and its daughter vessels. The outflow from each branch of the replica was controlled so that the infrarenal aortic flow rate and the flow partition at the aortic trifurcation were the same for all experiments. LDV measurements were made with flow exiting through both the renal and celiac artery ostia, only the celiac ostium, and neither ostium. The steady flow results indicate that while the outflow through the renal arteries did not have a significant effect on near wall shear rate in the external iliac arteries, the flow through the celiac artery did. However, in pulsatile flow, three indices of near wall velocity in the iliac arteries were unaffected by celiac artery outflow, while a fourth showed a small effect that can be attributed to differences in minimum velocity. These results indicate that reliable simulations of blood flow in the external iliac arteries can be carried out without including the renal and celiac vessels, provided that the correct infrarenal flow wave is used. They also demonstrate that the flow field downstream of a region, such as a branch, that strongly alters the flow, can be nearly independent of the velocity field entering the region.

Effect of periodic alterations in shear on vascular macromolecular uptake.

Experiments were carried out in swine to test the hypothesis that changes in the fluid dynamic environment of the arterial wall, with time constants of several minutes to perhaps a few hours, prompt adaptive responses that transiently increase endothelial permeability. After parenteral Evans Blue Dye (EBD) administration, the hemodynamics of the external iliac arteries of the experimental animals were altered using a reversible arteriovenous femoral shunt. For 3 h, the shunt was opened and closed with a period (tau) between 1-180 min. Subsequently, the animal was euthanized and the iliac vessels were photographed en face to obtain the distribution of EBD-bound albumin uptake by the tissue during its exposure to the dye. Albumin uptake increases with tau in a fashion that can be explained by an a priori model of the adaptive permeability response, with a time constant of about an hour.

Peritonectomy and intraperitoneal chemotherapy in appendiceal and colorectal cancer.

BACKGROUND: Peritoneal spread of gastrointestinal malignancies has been regarded as an incurable disease, and treatment has been aimed at short-term palliation. The use of cytoreductive surgery, including peritonectomy procedures and intraperitoneal chemotherapy, has been proposed with the intention of prolonging survival, and perhaps curing patients with peritoneal carcinomatosis from appendiceal and possibly colon cancers. A series of eight patients who have undergone this procedure at St George Hospital is presented, and the results obtained by other groups are reviewed. METHOD: Eight patients fitted the criteria for peritoneal carcinomatosis between January 1996 and November 1998. In seven patients this was secondary to appendiceal or colon cancer. and one patient had signet ring cancer of the uterus. The surgical treatment involved removing all macroscopic evidence of disease, and this was followed by early postoperative intraperitoneal chemotherapy. RESULTS: The eight patients (seven female, one male) ranged in age from 25 to 67 years. There were seven complications, including two patients with pelvic abscesses, and one patient who developed Tenchkoff catheter occlusion. There were three deaths, one due to pelvic sepsis after 30 days, and the other two were due to metastatic disease. Of the remaining five patients, two have developed recurrence and three remain disease-free. CONCLUSION: The results of peritonectomy and intraperitoneal chemotherapy for appendiceal tumours are encouraging. The role in colorectal cancer is less clear, although there are some reports that suggest a benefit.

Effect of alterations in femoral artery flow on abdominal vessel hemodynamics in swine.

In support of an in vivo investigation in swine of the influence of changes in fluid dynamic wall shear on arterial macromolecular permeability, a procedure has been developed to alter the flows in the porcine posterior arterial vasculature by opening and closing a reversible arteriovenous shunt placed on one of the femoral arteries. Laparoscopic techniques were used to place appropriately modified Transonic Systems ultrasonic flow probes on both external and circumflex iliac arteries, and on the terminal aorta. Flow measurements were made prior to shunt placement, and with the shunt open and closed, to measure the influence of altered external iliac artery flow on the distribution to the infrarenal abdominal vessels. Similar experiments were carried out to relate the flow rates in the external iliac arteries to those in the femoral arteries, which are more accessible. Based on the relationships among the measured flow rates, rules have been developed to estimate the major infrarenal flows in the pig, at baseline and with the shunt opened and closed, from only the flow rates measured at the two femoral arteries.

Radiologically placed hepatic artery catheter allows selection of patients with high-volume liver metastases for regional chemotherapy.

Regional chemotherapy has achieved high response rates in hepatic metastases from colorectal cancer and has been shown to improve survival significantly. The present paper reports the use of pre-operative regional therapy to establish marker response as a means of selection of patients for surgery. Fourteen patients underwent radiologically placed hepatic artery catheter (HAC) for chemotherapy. In the 11 patients with carcino-embryonic antigen (CEA) fall the patient proceeded to open surgical placement of HAC. The predictive effect of CEA fall following radiological HAC was good. Non-responding patients are clearly spared the discomfort and inconvenience and costs of an unnecessary operation.

Previous intravenous chemotherapy does not alter response rate or survival time of patients with hepatic metastases from colorectal cancer treated by hepatic artery chemotherapy.

BACKGROUND: The present paper addressed the issue of whether pretreatment with intravenous (i.v.) chemotherapy affects response rate or survival in patients receiving hepatic artery chemotherapy (HAC). METHODS: Case note reviews of 164 patients treated in a teaching hospital from June 1990 to July 1996 were carried out. RESULTS: The response rate and carcino-embryonic antigen (CEA) fall in the two groups was almost identical. There was a nonsignificant survival advantage in the non-pretreatment group. CONCLUSIONS: Previous administration of i.v. chemotherapy did not affect the CEA response of patients receiving HAC.

Major upper gastrointestinal haemorrhage associated with hepatic arterial chemoperfusion.

BACKGROUND: The present study reviews the nature of upper gastrointestinal complications of hepatic arterial chemoperfusion at a tertiary referral centre for the treatment of hepatic malignancy. METHODS: The patients involved in the present study all had major upper gastrointestinal (GI) haemorrhage and were undergoing hepatic arterial chemoperfusion. RESULTS: Eight patients had major upper GI haemorrhage. Three of these patients were not referred for surgical management, and all three patients died. The five patients who were admitted or transferred to our unit and who underwent surgery all survived. CONCLUSIONS: These complications are probably caused by extravasation of 5-fluorouracil (5-FU) following thrombosis of the gastroduodenal artery. The resulting cavity may perforate into the hepatic artery, portal vein, duodenum or biliary tree. Surgeons and oncologists should be aware of these complications. If upper abdominal pain occurs, chemoperfusion should cease immediately and an urgent investigation, which may include catheter angiography, gastroscopy and computed tomography (CT) scanning, should be carried out to exclude an hepatic artery pseudo-aneurysm.

An open multicentre study of tropisetron for cisplatin-induced nausea and vomiting.

OBJECTIVES: (i) To assess the efficacy and tolerability of tropisetron when used for acute and delayed cisplatin-induced emesis. (ii) To investigate whether dexamethasone added to tropisetron improves the control of emesis for patients who do not achieve a complete response to tropisetron alone. (iii) To assess sex of the patient and alcohol intake as prognostic factors for nausea and vomiting. DESIGN: A prospective open label phase II trial over one or two cycles of chemotherapy. Data collection was based on observed response and patients' self-reporting. SETTING: Twenty Australian tertiary care hospitals in 1994. PATIENTS: 102 male and female patients from 18 to 75 years with histologically confirmed malignancy receiving their first chemotherapy containing > or = 50 mg/m2 cisplatin. INTERVENTION: In Cycle 1 tropisetron 5 mg was given intravenously before chemotherapy on Day 1, then 5 mg orally before breakfast on Days 2 to 6. In Cycle 2, dexamethasone 20 mg intravenously on Day 1, then 8 mg orally on Days 2 to 6 could be added to tropisetron if a complete antiemetic response had not been achieved in Cycle 1. MAIN OUTCOME MEASURES: Number of vomiting episodes and severity of nausea for 6 days after chemotherapy; severity of side effects; patient satisfaction with chemotherapy treatment; oestradiol levels in women; and past alcohol consumption in men and women. RESULTS: (i) The complete response rate (CR) for acute emesis in Cycle 1 was 64% (95% confidence interval [CI], 54%-72%), with 84% (95% CI, 76%-90%) having < or = 2 vomits. The CR for delayed emesis was 24% (95% CI, 17%-32%). The CR for acute nausea was 56% (95% CI, 47%-66%), with 97% (95% CI, 91%-99%) having < or = 2 nausea episodes. The CR for delayed nausea was 21% (95% CI, 14%-30%). Seventy-one patients received Cycle 2. The main side effects were headache (20 patients) and constipation (16 patients). The control of acute emesis was rated as "good" or "very good" by 68% of investigators; 85% rated the tolerability of treatment as "good" or "very good". Treatment was rated as "very satisfactory" or "satisfactory" by 52% of patients. (ii) The CR for acute emesis with dexamethasone added was 78% (95% CI, 64%-88%). (iii) Women with lower oestradiol levels had better control of emesis, although this difference was not statistically significant. Chronic alcohol intake and binge drinking were strongly associated with a complete acute antiemetic response. CONCLUSIONS: Tropisetron was effective for acute cisplatin-induced emesis; adding dexamethasone enhanced this response. Both single and combined therapy had less effect on delayed emesis. The impact of alcohol on control of emesis is a chronic rather than acute phenomenon which requires prospective testing.