Twenty-one adult patients were randomised to receive ghrelin on days 1 and 8 and placebo on days 4 and 11 or vice versa, given intravenously over a 60-min period before lunch: 10 received 2 mg kg À1 (lower-dose) ghrelin; 11 received 8 mg kg À1 (upper-dose) ghrelin. Active and total ghrelin, growth hormone (GH), and insulin-like growth factor 1 levels were monitored at baseline (4 -5 days before day 1), during treatment days, and at end of study (day 17/18). Drug-related adverse events (assessed by NCI-CTC-toxicity criteria and cardiac examination) did not differ between ghrelin and placebo. No grade 3/4 toxicity or stimulation of tumour growth was observed. The peak increase of GH, a biological marker of ghrelin action, was 25 ng ml À1 with lower-dose and 42 ng ml À1 with upper-dose ghrelin. Morning fasting total ghrelin levels were higher (Po0.05) for upper-dose patients at end of study (3580 pg ml À1 ) than at baseline (990 pg ml À1 ). Insulin-like growth factor 1 levels did not change. At day 8, 81% of patients preferred ghrelin to placebo as against 63% at the end of study. Nutritional intake and eating-related symptoms, measured to explore preliminary efficacy, did not differ between ghrelin and placebo. Ghrelin is well tolerated and safe in patients with advanced cancer. For safety, tolerance, and patients' preference for treatment, no difference was observed between the lower-and upper-dose group.

In 407 patients with small-cell lung cancer (SCLC), 61 pretreatment variables were evaluated in a Cox multiple regression analysis to assess their prognostic value. All patients received short-term intensive regimens (cyclophosphamide, etoposide and methotrexate or ifosfamide and etoposide, both followed by thoracic irradiation if complete response was noted). Lactate dehydrogenase (p = 0.001), tumour stage (p = 0.0001), serum sodium (p = 0.0009), pretreatment Karnofsky performance score (p = 0.0121), alkaline phosphatase (p = 0.0186) and serum bicarbonate (p = 0.0321) were the important prognostic factors. Once these variables were taken into account no other variable provided additional prognostic information. A simple scoring system ("Manchester Score") using these variables was established and shows little loss of information compared to the Cox analysis. The score distinguishes 3 prognostic groups, the best of which contains all long-term survivors, whereas the bad prognostic group contains no patient surviving longer than one year. The scoring system may help to design new treatment strategies and may also facilitate the comparison of different studies.

The dose level of ifosfamide 10 g/m2 and doxorubicin 90 mg/m2 with supportive GM-CSF is manageable in a multicenter setting and should be further tested in regular phase II trials, including patients with gynecological and soft-tissue sarcomas. Transient toxicity with myelosuppression should be accepted in order to obtain a high antitumor activity of this regimen and a potential improvement in survival.

Although some patients may have had useful palliation, JM216 did not appear to have significant antitumour activity in non-small-cell lung cancer.

The effect of age on the pharmacokinetics of ifosfamide was studied in 20 patients with advanced non small cell lung cancer. A positive correlation was found between the elimination half-life of ifosfamide and age (r = 0.48, 0.05 < P < 0.01). This was due to an increase in volume of distribution with age (r = 0.66, 0.001 < P < 0.01). Total plasma clearance, renal clearance and non renal clearance did not change with age. Age did not affect the autoinduction of ifosfamide metabolism. Further studies are needed to demonstrate any adverse effects of ifosfamide in the elderly.