In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival. (Current Controlled Trials number, ISRCTN93793971 [controlled-trials.com].).

The ECF regimen results in a survival and response advantage, tolerable toxicity, better QL and cost-effectiveness compared with FAMTX chemotherapy. This regimen should now be considered the standard treatment for advanced esophagogastric cancer.

Summary Extramedullary plasmacytomas (EMP) of head and neck are rare tumours. Between 1972 and 1993, 25 cases of EMP of head and neck were seen at our institute. The clinical and pathological features and response to treatment are presented. At initial presentation, 23 (92%) patients presented with disease confined to a single extramedullary site only and two patients had in addition clinical involvement of cervical lymph nodes. All except these two patients received radiotherapy to the primary site only as initial treatment. Initial primary control of local disease was obtained in 16 of 24 (67%) patients treated with radical intent. With salvage treatment of further radiotherapy and/or chemotherapy, local disease control was achieved in 21 of 24 (88%) patients. One patient was treated with palliative intent. Conversion to multiple myeloma was seen in two patients (8%). Pathologically, the tumours were classified into low, intermediate and high grade, which correlated closely with outcome. This classification has been used for the first time in extramedullary plasmacytomas and is based on the multiple myeloma grading criteria devised by Bartl et al (1987). Fifteen of eighteen (83%) low-grade tumours and only one of six (17%) intermediate-and high-grade tumours were locally controlled after primary radiotherapy. This is statistically significant for local control (P= 0.0019) but not for overall survival (P= 0.12). The median survival and 5-year overall survival is 68 months and 58.9% respectively. We recommend consideration of adjuvant chemotherapy in patients with higher grade disease.

The value of combination chemotherapy in advanced oesophagogastric cancer has been clarified. Three randomized clinical trials have demonstrated the superiority of chemotherapy over best supportive care alone (Murad et al, 1993;Pyrhonen et al, 1995;Glimelius et al, 1997). However, the optimal regimen has not yet been established. The combination of 5-fluorouracil (5-FU), adriamycin and methotrexate (FAMTX) has been considered standard therapy, with superior response and survival rates compared with previous regimens (Wils et al, 1991;Kelsen et al, 1992). A combination of cisplatin, epirubicin, leucovorin and 5-FU (PELF) has also demonstrated impressive response rates in a randomized study (Cocconi et al, 1994). The regimen of epirubicin, cisplatin and 5-FU (ECF) was developed at the Royal Marsden Hospital (RMH) and first reported in 1991 (Cunningham et al, 1991). The three drugs in this regimen were selected on the basis of their single agent activity in upper gastrointestinal tract tumours (Beer et al, 1983;Cersosimo and Hong, 1986;Machover et al, 1986), and on the synergy demonstrated between 5-FU and cisplatin in preclinical models (Etienne et al, 1991). The 5-FU is delivered as a protracted infusion as this schedule has produced higher response rates with less myelotoxicity compared with bolus administration in patients with colorectal cancer (Lokich et al, 1989). Following the demonstration of response rates of 71% with moderate toxicity in a phase II study (Findlay et al, 1994), we undertook a multicentre randomized study comparing ECF with FAMTX in advanced oesophagogastric cancer. The initial results of this trial were reported in 1996 when recruitment was completed (Webb et al, 1997). At that stage, an advantage for ECF in response rate and survival was evident. However, median follow-up was only 6.1 months and only 75% of patients had died. We now present a final survival analysis with all patients followed up for 26.9 months or more (median 44 months), and 95% of patients having died. METHODSOur methods have been described previously (Webb et al, 1997). Briefly, patients with inoperable adenocarcinoma or undifferentiated carcinoma of the oesophagus, oesophagogastric junction, or stomach were randomized to receive ECF or FAMTX chemotherapy. ECF chemotherapy was administered through a central venous catheter placed in the subclavian vein. 5-FU was given as a continuous intravenous infusion at a dose of 200 mg m -2 day -1 for up to 6 months. Epirubicin (50 mg m -2 ) and cisplatin (60 mg m -2 ) were given every 3 weeks to a maximum of 8 cycles. FAMTX chemotherapy comprised methotrexate 1500 mg m -2 and 5-FU 1500 mg m -2 on day 1, and doxorubicin 30 mg m -2 on day 15. Cycles were repeated every 28 days to a maximum of 24 weeks. Patients were followed up with clinical and symptomatic SummaryWe report the final results of a prospectively randomized study that compared the combination of epirubicin, cisplatin and protracted venous infusion fluorouracil (5-FU) (ECF regimen) with the standard combination of 5-...

Summary. Four hundred and twenty-nine patients received myeloablative chemotherapy for solid and haematological malignancies in a bone marrow transplantation unit. Regimens appropriate to the tumour type were administered and haemopoietic reconstitution was achieved with peripheral blood progenitor cells (PBPC; n 275), autologous bone marrow (auto-BMT; n 69) or allogeneic bone marrow (allo-BMT; n 85). World Health Organization (WHO) oral mucositis scores were collected prospectively from the start of chemotherapy (d 1) until d 28 or discharge. Oral mucositis (OM) was experienced by 425 (99%) patients and in 289 (67´4%) this was grade III or IV. Strong opiate analgesia was prescribed for a median of 6 d to 47% of patients. Univariate analysis suggested that the area under the OM curve (AUC; sum of daily mucositis grades, d 1±28) was associated with the myeloablative regimen, haemopoietic progenitor source (PBPC . allo-BMT . auto-BMT), use of myeloid growth factors and age. Multivariate analysis showed that the only independent risk factor for mucositis was the conditioning regimen (P , 0´00005). The mean OM AUC for high-dose melphalan (HDM) regimens (52 grade±days) exceeded busulphan (41), busulphan±cyclo-phosphamide (35), cyclophosphamide±total body irradiation (TBI) (34), cyclophosphamide±carmustine (BCNU) (20) and cyclophosphamide±etoposide±carmustine (CVB) (19). HDM regimens resulted in the highest mean peak OM (3´6), followed by busulphan regimens (2´6), cyclophosphamide/TBI (2´3) and cyclophosphamide±carmustine and CVB (1´4). Busulphan produced significantly delayed OM (median 3 d; P , 0´00005). There was a linear association between the area under the OM curve for each treatment group and the time to reach grade 3 OM (P , 0´00005), but no association with the time to reach grade 4 neutropenia (P 0´24) or thrombocytopenia (P 0´73), implying that haematological and mucosal toxicity are not associated. The cytotoxic regimen is the most significant determinant of OM. Studies investigating agents to ameliorate mucosal toxicity should be stratified according to cytotoxic regimen.

Vaccination against influenza and Streptococcus pneumoniae is recommended for elderly and immunocompromised individuals. However, there is little information concerning the efficacy of vaccination in specific groups of patients. In this study, 52 patients underwent vaccination against influenza, S. pneumoniae and Haemophilus influenzae type b (Hib) as they attended hospital outpatient clinics. Serum was analysed prior to vaccination and 4–6 weeks afterwards. Antibody titres against S. pneumoniae and Hib were compared with reference values corresponding to the geometric mean titres of a healthy UK population. For influenza vaccination, haemagglutination inhibition (HI) titres were measured against three inactivated strains; a titre of ≥ 1/40 was considered protective. No patient had protective titres to all three antigens prior to vaccination and 41 patients (85%) had titres < 1/40 to all 3 strains. Post vaccination only 9/48 patients (19%) achieved protective antibody titres. Resistance to S. pneumoniae and response to Pneumovax II was also poor: prevaccination, 45 patients (93%) had suboptimal antibody titres and in 26/43 patients (61%) titres remained low post vaccination. Resistance to Hib and response to vaccination was comparable with the healthy adult UK population. These results question the practice of routine influenza and pneumococcal vaccination in myeloma patients. © 2000 Cancer Research Campaign

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Summary:Liposomal amphotericin (AmBisome) 2 mg/kg three times weekly was compared with placebo as prophylaxis against fungal infection in patients undergoing chemotherapy or bone marrow transplantation (BMT) for haematological malignancies. Prophylaxis began on day 1 of chemotherapy and continued until neutrophils regenerated or infection was suspected. Of 161 evaluable patients, 74 received AmBisome and 87 received placebo. Proven fungal infections developed in no patients on AmBisome and in three on placebo (3.4%) (P ‫؍‬ NS). Suspected fungal infections requiring intervention with systemic antifungal therapy (usually amphotericin B) occurred in 31 patients on AmBisome (42%) and in 40 on placebo (46%) (P ‫؍‬ NS). Suspected deep-seated infections developed in 21 (28.3%) and 31 (35.6%) patients, respectively (P ‫؍‬ NS). Time to develop a suspected or proven deep-seated infection showed a trend in favour of AmBisome (P ‫؍‬ 0.11). Fifty patients had fungal colonisation (48 with Candida spp, two with Aspergillus spp) of at least one body site during prophylaxis; 15 patients while receiving AmBisome (20%) and 35 while on placebo (40%) (P Ͻ 0.01). Time to colonisation was significantly delayed in the group receiving AmBisome (P Ͻ 0.05). Treatment-related toxicity was modest and no additional toxicity was observed in patients receiving AmBisome. AmBisome 2 mg/kg three times weekly is safe and reduces fungal colonisation in patients receiving intensive chemotherapy or BMT. However, despite encouraging trends, prophylactic AmBisome did not lead to a significant reduction in fungal infection or in requirement for systemic antifungal therapy. Keywords: AmBisome; prophylaxis; neutropenia More than half the fatal infections in neutropenic patients are due to fungi 1 with candida and aspergillus the most commonly-observed pathogens. fungal infection increases with the severity and duration of neutropenia which, in the case of bone marrow transplantation (BMT) or chemotherapy for the treatment of haematological malignancies, can range from a few days to several weeks. The severe immunosuppression induced by high-dose corticosteroids given to recipients of allogeneic BMT to suppress graft-versus-host disease (GVHD) puts them at additional risk of fungal infections 2-4 whereas for patients receiving autologous stem cell support and treatment with growth factors the risk is much lower.5 This provides a rationale for the prophylactic use of antifungal agents.Orally administered agents such as the imidazoles, or non-absorbable amphotericin B, achieve only local decontamination and have little or no impact on invasive fungal infections. 6 A recent meta-analysis 7 has been conducted of 24 trials in which antifungals were used, either as prophylaxis or as empirical therapy, in patients with cancer complicated by neutropenia. This meta-analysis showed that amphotericin B decreased mortality significantly although the studies were small, as was the difference in the number of deaths. Antifungals as a group decreased the incidence of inv...