Objective: Zidovudine (ZDV) is the only antiretroviral drug which has been shown to reduce mortality in patients with symptomatic HIV disease, but its use is restricted by intolerance in a significant proportion of patients. Additionally, the efficacy of ZDV therapy appears to decrease after prolonged treatment particularly in the advanced stage of HIV disease. Therefore, alternative antiretroviral regimens for patients are needed. In this study, didanosine (ddl; 2',3'-dideoxyinosine), another HIV reverse transcriptase inhibitor, was evaluated.Design: A total of 426 patients with AIDS or AIDS-related complex (ARC) who were intolerant to or clinically progressing on ZDV therapy and who had CD4+ cell counts less than or equal to 150 x 10(6)/l were randomized to receive either a high (750 mg for bodyweight greater than or equal to 60 kg or 500 mg for bodyweight < 60 kg) or a low (200 mg and 134 mg, respectively) dose of ddl daily.Setting: The patients were recruited from 31 German and Austrian AIDS clinical primary-care centres.Results: The study was stopped after the second interim analysis due to a statistically significant difference in the incidence of pancreatitis (nine versus 26; relative risk, 2.92; P=0.003) and neuropathy (28 versus 43; relative risk, 1.55; P=0.05) in favour of the low dose. There was no difference between the low and high dosage groups in survival rate at 6 (80 versus 80%) and 12 months (61 versus 65%), number of deaths [82 (43.6 per 100 patient-years) versus 84 (44.4 per 100 patient-years)], progression from ARC to AIDS or to AIDS or death, or average number of new/recurrent opportunistic infections (2.8 versus 3.0 per patient).Conclusions: This study cannot conclude on ddl efficacy but it shows that in patients with advanced HIV disease for whom no alternative antiretroviral therapy is available and ddl therapy is considered, daily doses < 750 mg should be administered.

Doxifluridine (5'dFUR) is a new fluoropyrimidine derivative with significant antitumor activity in animal models. Preliminary studies with bolus injections, one, six hours and continous infusion, have indicated that doxifluridine is active in a variety of refractory tumors. In a randomized multicentre trial 71 previously untreated patients with advanced colorectal carcinoma were allocated to receive doxifluridine (5'dFUR) 4,000 mg/m2 or 5-fluorouracil (5-FU) 450 mg/m2 as one hour intravenous infusion daily for 5 consecutive days every 4 weeks. In 61 evaluable patients (5'dFUR 31 and 5-FU 30) non-complete remission was treated with 5'dFUR and 2/30 (7%) of patients treated with 5-FU. The median survival of the 5'dFUR arm (all patients) was not statistically different compared to 5-FU (52.5 and 42.5 weeks).Gastrointestinal adverse events were common in both treatment groups. Hematotoxicity occurred in both schedules with a higher incidence for the 5'dFUR arm. Additionally, low grade toxicity (WHO grade 1-2) of skin, neurotoxic symptoms and cardiotoxicity occurred in the 5'dFUR arm only.5'dFUR in dosage and schedule used in this study is an active agent for advanced colorectal carcinoma but efficacy is accompanied by more pronounced adverse reactions.

Eine der bemerkenswerten Folgen der HIV-Infektion sind maligne Tumoren. Das an sich seltene Kaposi-Sarkom gehörte neben der Pneumocystis-carinii-Pneumonie zu den ersten Aids-identifizierenden Indikatorkrankheiten [2]. Das Kaposi-Sarkom ist auch weiterhin der häufigste Aids-assoziierte maligne Tumor.

27 patients with advanced colorectal cancer were treated in a phase-II trial with high dose sequential methotrexate (MTX), 5-fluorouracil (5-FU), and folinic acid (FA). Following a 4 h infusion of 800 mg/m2 MTX and a 4 h interval, 1,500 mg/m2 5-FU and 200 mg/m2 FA were given as a 24 h infusion. Out of 23 evaluable patients we observed one partial remission and 9 disease stabilizations. Median survival time of all patients was 10.4 months. Overall toxicity was low. In comparison to a previous trial we did not observe better treatment results by adding high dose FA to a sequential MTX/5-FU schedule.

Doxifluridine, a new fluoropyrimidine analog, was administered to 21 patients with advanced colorectal carcinoma. The starting dose was 1.0 g/m2 given over 24 h for 90 consecutive days as a continuous infusion. Due to severe skin reactions (hand-foot syndrome), the dose was reduced stepwise to 0.75 g/m2/day. Twenty patients were evaluable for efficacy, one had an early non-toxic death. Seven out of 20 (35%) showed a partial response; disease stabilization was observed in 10 patients (50%) and three showed progressive disease after 3 months of treatment. All 17 patients who achieved a partial response or a stabilization of disease were treated until progressive disease was documented and some had therapy up to 46 weeks. Toxicity was minimal and mainly defined as hand-foot syndrome which occurred in 50% of the patients of whom three experienced severe reaction. There was no myelosuppression, renal or liver dysfunction, no cardiac alterations and only one patient experienced severe dizziness. Doxifluridine is active in advanced colorectal carcinoma when the drug is given as a continuous infusion for 90 consecutive days at a daily dose of 0.75 g/m2.

Die Haarzelleukämie wurde mit α-2-Interferonen nach zwei aufeinander abgestimmten Therapieprotokollen behandelt. Die Wirksamkeit niedriger Tagesdosen konnte belegt werden und ebenso die geringe Rate an Nebenwirkungen. Die niedrigen Dosen verbesserten bei täglicher Applikation die hämatologischen und klinischen Parameter rasch, erzeugten aber eine erhöhte Anfälligkeit für tödliche Infektio-nen bei Splenektomierten. Eine ebenso niedrig dosierte pulsatile Therapie wurde in das 2. Protokoll mit einem klar abgesetzten zeitlichen Verhalten für die Splenektomierten eingesetzt, um die Bedeu-tung einer rhythmischen Applikation abschätzen zu lernen. Sie hat sich inzwischen und vorläufig als wirksam und sicher erwiesen. Die weitere Entwicklung sicherer und nebenwirkungsarmer Therapien für die HCL bleibt das Hauptziel der Studiengruppe. Der Stellenwert des bisher in der Rezidivbehandlung eingesetzten Desoxicoformicins [4, 7] wird noch zu erarbeiten sein.

Within less than 14 months of recruitment 32 centers enrolled 97 patients in a multicenter trial for low-dose treatment of hairy cell leukemia (1.2 X 10(6) IU/m2 X 28 days s.c. with dose reduction according to clinically judged improvement) or ultra-low dose treatment (1.2 X 10(5) IU/m2, s.c. daily increasing to a well-tolerated dose) with Hr IFn-2c (arg). Induction therapy was limited to 84 days. Patients who reached the clinical stage Jansen I or A were then randomized to 2 arms either to receive further IFn (1.2 X 10(6) IU/m2 s.c.) twice a week or to be taken off treatment. For both arms induction therapy was reinstituted whenever a patient lost the criteria of Jansen stage A or I. The study included obligatory central diagnostic procedures and several special investigations. During the first year of the study a special problem evolved in the group of 34 patients with recurrent disease after splenectomy. Ten of them died, 9 of septicemia and 1 of bleeding complications, whereas only 1 death occurred in those patients who received IFn before splenectomy. The risk factors and the response to therapy in the two groups will be analyzed in order to define the criteria that will be needed for the proper choice of primary treatment for HCL. It appears important to us to restrict splenectomy to selected patients.

Our multicenter study on the treatment of hairy cell leukemia (HCL) started in December 1984 and the present data cover the time up to June 30, 1986. Ninety-seven patients were enrolled. For induction of response daily doses (6 micrograms) of low dose human recombinant alpha 2c-interferon (arg) was chosen. Further dose reduction (3 micrograms) was possible for patients who improved within the first 3-4 weeks. Patients with known risk factors started at lower doses (0.6 microgram daily). As infections are known to be the main cause of death in HCL, splenectomy was not mandatory before treatment. Thirty-nine patients received treatment with interferon. Nevertheless, infections remained the major cause of death in the study. The protocol did not prevent fatal infections in nine of the 34 splenectomized patients. The regimen proved safe for all but one of the nonsplenectomized patients. According to this experience, new criteria are needed for the choice of primary treatment in HCL. In our opinion splenectomy should become restricted to selected cases.

Innerhalb von weniger als 14 Monaten brachten 32 Kliniken 97 Patienten in eine multizentrische Studie zur Prüfung einer niedrigdosierten Interferonbehandlung der Haarzelleukämie ein. Verwendet wurden 1,2 ×106 IU/m2 (humanes Rekombinanten-Interferon-Alpha 2c arg (Hr IFn – 2c (arg)) x 28 Tage s.c. mit vereinbarter Reduktion der Dosis nach Eintritt einer klinischen Besserung oder eine ultraniedrige Dosis von 1,2×106 IU/m2 s.c. täglich und sich steigernd bis zu einer gut tolerierten Dosis. Die Induktionsphase war auf 84 Tage begrenzt. Patienten, die in diesem Zeitraum das klinische Stadium Jansen I oder A erreichten, wurden randomisiert und in zwei Armen der Erhaltungstherapie zugeführt. Ein Teil der Patienten erhielt wei-terhin Interferon (2× wöchentlich), die anderen wurden ohne Therapie belassen. Für alle Patienten sollte die Therapie wieder eingesetzt werden, wenn die Jansen-Stadien A oder I verlorengingen. Die Studie umschloß obligatorische zentrale diagnostische Maßnahmen zur Sicherung der Diagnose und Messung des Therapieerfolgs. Während der Laufzeit entwickelte sich eine besondere Problematik in der Gruppe der 34 Patienten mit wiederkehrendem © 1987 S. Karger AG, Basel Article / Publication Details First-Page Preview Published online: April 24, 2009 Issue release date: 1987 Number of Print Pages: 6 Number of Figures: 0 Number of Tables: 0 ISSN: 2296-5270 (Print) eISSN: 2296-5262 (Online) For additional information: https://www.karger.com/ORT

In a prospective study, 156 patients with advanced lung and gastrointestinal carcinomas, receiving palliative chemotherapy or radiotherapy, were examined for changes in their quality of life during therapy. A questionnaire (68 questions), a linear analogue scale, and the Karnofsky performance scale were used three times in the course of therapy. The most important result seen during the evaluation of the questionnaire was the improvement in the psychical state in patients with tumor remission, even with increasing side-effects. In patients with progressive disease, a deteriorated psychosocial state and an increased burden due to the toxic side effects were observed. These results were also confirmed in progressive patients by the linear analogue scale. The Karnofsky performance scale showed a high correlation for the judgement of disease-related contents and the activity of the patient. In this study the relationship of treatment results and well-being is shown. It would seem important to include methods for the measurement of quality of life for the evaluation of oncological therapies.