Chemoradiotherapy with concurrent gemcitabine and cisplatin with or without sequential chemotherapy with gemcitabine/cisplatin vs chemoradiotherapy with concurrent 5-fluorouracil in patients with locally advanced pancreatic cancer--a multi-centre randomised phase II study.

BACKGROUND: No standard treatment for locally advanced pancreatic cancer (LAPC) is defined. PATIENTS AND METHODS: Within a multi-centre, randomised phase II trial, 95 patients with LAPC were assigned to three different chemoradiotherapy (CRT) regimens: patients received conventionally fractionated radiotherapy of 50 Gy and were randomised to concurrent 5-fluorouracil (350 mg m(-2) per day on each day of radiotherapy, RT-5-FU arm), concurrent gemcitabine (300 mg m(-2)), and cisplatin (30 mg m(-2)) on days 1, 8, 22, and 29 (RT-GC arm), or the same concurrent treatment followed by sequential full-dose gemcitabine (1000 mg m(-2)) and cisplatin (50 mg m(-2)) every 2 weeks (RT-GC+GC arm). Primary end point was the overall survival (OS) rate after 9 months. RESULTS: The 9-month OS rate was 58% in the RT-5-FU arm, 52% in the RT-GC arm, and 45% in the RT-GC+GC arm. Corresponding median survival times were 9.6, 9.3, and 7.3 months (P=0.61) respectively. The intent-to-treat response rate was 19, 22, and 13% respectively. Median progression-free survival was estimated with 4.0, 5.6, and 6.0 months (P=0.21). Grade 3/4 haematological toxicities were more frequent in the two GC-containing arms, no grade 3/4 febrile neutropaenia was observed. CONCLUSION: None of the three CRT regimens tested met the investigators' definition for efficacy; the median OS was similar to those previously reported with gemcitabine alone in LAPC.

Value of a multileaf prescription preparation system for palliative external beam irradiation.

In palliative treatment, irregularly shaped fields are used to reduce side-effects and can improve, or avoid, field matching. We investigated the effectiveness of a multileaf collimator (MLC) supported by a digitizing data entry system in the palliative radiotherapy treatment of 66 patients and compared it with conventional shielding with geometrically shaped blocks. After conventional simulation of rectangular fields, irregular field shapes were marked on the simulator film in 17 patients (27%) to reduce radiotherapy related side-effects. Individual leading was performed with an MLC. Digitizing and fitting of the optimum leaf position were carried out using a multileaf preparation system (MLP, Elekta, Crawley, UK). Target volumes included bone metastases in the pelvis, spine and extremities, mediastinal soft tissues, lymph nodes and central nervous system. In 10 patients, treated with a parallel pair for pelvic metastases, MLC and conventional shielding were prospectively compared with regard to time requirements and area shielded. Compared with conventional blocking, the mean simulation, preparation and treatment time required for MLP fields was shorter (9.55 +/- 1.44 min vs 16.90 +/- 2.64 min, and 5.50 +/- 1.14 min vs 8.97 +/- 1.75 min). The mean shielded area was 31 cm2 larger for MLC fields compared with geometrically shaped blocks (p < 0.05). Compared with cerrobend blocking, the use of an MLC, supported by preparation data entry software, is more flexible and reduces radiotherapy resources. Therefore, a preparation data entry system as a separate device, or integrated into the treatment planning system, is a useful tool in palliative treatment.

Povidone-iodine to prevent mucositis in patients during antineoplastic radiochemotherapy.

In an open study, the efficacy of povidone-iodine in the prophylaxis of mucositis during antineoplastic radiochemotherapy was determined. 40 patients were randomly assigned to a treatment or control group (each 20 patients). All patients received standard prophylaxis of mucositis with nystatin, dexpanthenol, rutoside and immunoglobulin. In addition, the patients of the treatment group performed 4 times daily rinsing with povidone-iodine, the control patients with sterile water. Clinical examination of the oral mucosa was performed weekly during the radiation period and up to 6 weeks after the end of therapy. Oral mucositis was observed in 14 patients of the treatment group (mean grading: 1.0) and in all 20 patients of the control group (mean grading: 3.0). The mean onset of mucositis was after 2.25 weeks in treatment patients and 1.5 weeks in control patients. The mean total duration of mucositis was 2.75 weeks in treatment patients and 9.25 weeks in control patients. The mean AUC values were 2.5 in treatment patients and 15.75 in control patients. All findings were statistically significantly different between the two groups. It is concluded that rinsing with povidone-iodine reduces the incidence, severity and duration of oral mucositis during antineoplastic radiochemotherapy.

Comparison of two strategies for the treatment of radiogenic leukopenia using granulocyte colony stimulating factor.

PURPOSE: Radiation-induced leukopenia can cause a delay or discontinuation of radiotherapy. This complication can be overcome with the use of granulocyte colony-stimulating factor (G-CSF). However, an uncertainty exists regarding the mode of application of G-CSF in patients treated with radiotherapy. For this reason, the efficacy of two strategies for the administration of G-CSF in irradiated patients was compared in a prospective randomized clinical study. METHODS AND MATERIALS: Forty-one patients who developed leukopenia (< 2.5 x 10(9) per liter) while undergoing radiotherapy were treated with G-CSF at a daily dose of 5 microg/kg. The first group received single injections of G-CSF as required (n = 21). The second group received G-CSF on at least 3 consecutive days (n = 20). An analysis was made of the changes in leukocyte counts, the number of days on which radiotherapy had to be interrupted, and the side effects of growth-factor treatment. RESULTS: An increase in leukocyte values in the peripheral blood was observed in all patients treated with G-CSF. In the group which received G-CSF when required, two injections (range: 1-8) were administered in most cases. In the second group, most of the patients received three injections (range: 3-9). The average duration of therapy interruptions due to leukopenia was 4.8 days (0-28) in the first therapy arm and 2.5 (0-20) in the second arm. The variance in the duration of therapy interruptions between the two groups was not significant (p = 0.2). Radiotherapy had to be terminated in two patients due to thrombocytopenia but the application of G-CSF did not seem to be a reason of decreasing platelet counts. CONCLUSIONS: Our results reveal that G-CSF is safe and effective in the treatment of radiation-induced leukopenia regardless of the mode of application. Because the calculated difference related to radiation treatment interruptions has no clinical relevance, both approaches examined in our study appear reasonable.