Biochemotherapy with low doses of subcutaneous interleukin-2 in patients with melanoma: results of a phase II trial

Introduction Metastatic melanoma has an ominous prognosis. Bio-chemotherapy regimens can increase the response rate but with a high degree of toxicity due, mainly, to the use of high-dose intravenous interleukin-2. Objectives To test the feasibility and activity profile of a bio-chemotherapy regimen of low-dose subcutaneous interleukin-2. Material and methods Administration scheme: dacarbazine at 200 mg/m²/d on days 1–4, cisplatin at 20 mg/m²/d intravenous on days 1–4, vinblastine at 1.5 mg/m²/d on days 1–4, IL-2 at 4.5 MUI/m²/d subcutaneous on days 5–8, IFN-alpha at 5 MU subcutaneous on days 5–9, 11, 13, 15 of every 21-day cycle. Results Objective response was obtained in 11 patients (39.3%; 95%CI: 21–59) including 4 with complete response (14.5%; 95%CI: 4–33). With an extended follow-up of 49 months and 60 months, respectively, 2 patients continue with complete response. The main toxicities were haematological: grade 3–4 neutropenia in 8.2% of cycles, thrombocytopenia in 1.2% and anaemia in 3.2%. Conclusions The regimen is safe and has a good activity profile. The presence of long-term survivors, despite the use of lower doses and subcutaneous IL-2, is encouraging.     

Five-year results of combined chemotherapy and mediastinal radiation therapy in small cell lung cancer

Eighty-five patients with small cell lung cancer (limited disease = LD in 39, extensive disease = ED in 46) received the combination of cyclophosphamide, methotrexate, vincristine and CCNU, and mediastinal radiotherapy given simultaneously after the third course of chemotherapy. The duration of treatment was approximately 12 months. A complete response was obtained in 41% of LD and in 15% of ED patients, and a partial response in 38 and 22%, respectively. Median survival was 55 weeks for LD and 37 weeks for ED patients. Two patients (5%) with LD have survived free of disease more than 3 years since their diagnosis.     

Randomised study of tegafur and oral leucovorin versus intravenous 5-fluorouracil and leucovorin in patients with advanced colorectal cancer

This randomised, open-label trial compared oral tegafur (FT)/leucovorin (LV) with the intravenous bolus 5-fluorouracil (5-FU)/LV as first-line chemotherapy for advanced colorectal cancer (CRC). Patients were randomised to receive oral FT 750 mg/m2/day for 21 days and LV 15 mg/m2 every 8 h in cycles repeated every 28 days (n=114), or intravenous LV 20 mg/m2 followed by 5-FU 425 mg/m2 daily for 5 days every 4 weeks for 2 cycles, and later every 5 weeks (n=123). Response rate was significantly higher in the FT/LV arm (27%, 95% CI 19-35) than in the 5-FU/LV arm (13%, 95% CI 7-19) (p<0.004). The median time to progression was 5.9 months (95% CI, 5.3-6.5; FT/LV arm) and 6.2 months (95% CI, 5.4-6.9; 5-FU/LV arm). Median overall survival was 12.4 months (95% CI, 10.3-14.5 months; FT/LV arm) and 12.2 months (95% CI, 8.9-15.7 months; 5-FU/LV arm) (p=n.s.; hazard ratio FT/LV:5-FU/LV=1.02). 5-FU/LV showed a higher incidence of grade 3/4 neutropenia (4.1 vs. 0%). Non-hematological toxicities showed similar incidences in the two treatment arms. Oral FT/LV was more active than IV 5-FU/LV in terms of objective response rate with similar overall survival, and with a favorable toxicity profile. This makes FT/LV a valid alternative to the IV 5-FU schedule in CRC patients.     

Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER-2/neu transgenic mice

Female FVB/N HER-2/neu transgenic mice from the age of 2 months were subcutaneously injected with saline, the peptide Epitalon(R) (Ala-Glu-Asp-Gly) or with the peptide Vilon(R) (Lys-Glu) in a single dose of 1 microg/mouse for 5 consecutive days every month. Epitalon treatment reduced the cumulative number and the maximum size of tumors (p < 0.05). Furthermore, the number of mice bearing 1 mammary tumor was increased, whereas the number of mice bearing 2 or more mammary tumors was reduced in Epitalon-treated in comparison to saline-treated animals (p < 0.05). The size but not the number of lung metastases was reduced in Epitalon-treated compared to saline-treated mice (p < 0.05). The treatment with Vilon produced significant negative effects when compared to the control group, with an increased incidence of mammary cancer development (p < 0.05), a shorter mean latent period of tumors (p < 0.05) and an increased cumulative number of tumors (p < 0.05). A 3.7-fold reduction in the expression of HER-2/neu mRNA was found in mammary tumors from HER-2/neu transgenic mice treated with Epitalon compared to control animals. The expression of mRNA for HER-2/neu was also partially reduced in Vilon-treated mice, but it remained significantly higher in Vilon- than in Epitalon-treated animals (1.9-fold increase). The data demonstrate the inhibitory effect of Epitalon in the development of spontaneous mammary tumors in HER-2/neu mice, suggesting that a downregulation of HER-2/neu gene expression in mammary adenocarcinoma may be responsible, at least in part, for the antitumor effect of the peptide.     

Efficacy and safety of endoscopic balloon dilation in inflammatory bowel disease: results of the large multicenter study of the ENEIDA registry

Surgical Endoscopy - There is no information regarding the outcome of Crohn’s disease (CD) patients treated with endoscopic balloon dilation (EBD) in non-referral hospitals, nor on the...     

Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre la monitorización,prevención y tratamiento de la recurrencia posquirúrgica en la enfermedad de Crohn

Despite the availability of new, powerful drugs for Crohn's disease, a significant proportion of patients will undergo an intestinal resection to control the disease as it develops. In the absence of an effective preventative treatment, the appearance of new intestinal lesions after surgery for Crohn's disease is the norm; this is known as post-operative recurrence and may appear very early on, even a few weeks after the surgical resection. Furthermore, the drugs that are currently available for the prevention of post-operative recurrence have a limited effect; up to 50% of cases present recurrent Crohn's disease activity despite the preventative treatment, which may require further surgery with the consequent loss of intestinal function, leading some patients to suffer from short bowel syndrome as an irreversible complication. The management of Crohn's disease patients who undergo an intestinal resection should thus be geared towards prevention, early detection and, in the worst case scenario, the treatment of post-operative recurrence. This article reviews the natural history, diagnostic measures, monitoring, prevention and treatment of post-operative recurrence, and proposes recommendations based on existing knowledge.     

Use of granulocyte/monocytapheresis in ulcerative colitis: A practical review from a European perspective

Half of the patients with ulcerative colitis require at least one course of systemic corticosteroids in their lifetime. Approximately 75% of these patients will also require immunosuppressive drugs (i.e., thiopurines or biological agents) in the mid-term to avoid colectomy. Immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and co-morbid patients, underlining the unmet need for safer alternative therapies. Granulocyte/monocytapheresis (GMA), a CE-marked, non-pharmacological procedure for the treatment of ulcerative colitis (among other immune-mediated diseases), remains the only therapy targeting neutrophils, the hallmark of pathology in ulcerative colitis. GMA has proven its efficacy in different clinical scenarios and shows an excellent and unique safety profile. In spite of being a first line therapy in Japan, GMA use is still limited to a small number of centres and countries in Europe. In this article, we aim to give an overview from a European perspective of the mechanism of action, recent clinical data on efficacy and practical aspects for the use of GMA in ulcerative colitis.