European Journal of Cancer and Clinical Oncology最新文献

Recombinant interleukin-2 (rIL-2) has been reported to be active in metastatic renal cell carcinoma and malignant melanoma. The purpose of this trial was to determine the efficacy and toxicity of rIL-2 administered in continuous infusion in patients with Hodgkin's disease (HD) and non-Hodgkin lymphoma (NHL). 21 patients with HD (4 patients), diffuse large-cell NHL (7) or low-grade NHL (10) in failure or relapse after multiple-conventional treatments were included in this trial. rIL-2 therapy consisted of an induction period of two cycles separated by 3 weeks of rest, and, in the absence of progressive disease or undue toxicity, a maintenance period of 4 monthly cycles. Each induction cycle comprised the continuous infusion of rIL-2: 18 × 10⁶ IU/m² per day on days 1–5 and days 12–16. Each maintenance cycle comprised the continuous infusion of rIL-2: 18 × 10⁶ IU/m² per day on days 1–5. Among the 21 treated patients, 5 (all of those with low-grade NHL) responded to the induction phase (1 complete response, 4 partial responses) and 2 patients had a mixed response. Conversely, no response was observed in patients with HD or large-cell NHL. The median duration of response was 4 months. rIL-2 administered as a continuous infusion was well tolerated and most patients received the full dosage, and management did not require intensive care. During the induction period, 2 patients experienced grade III cardiovascular or renal toxicity. During the maintenance period, rIL-2 had to be interrupted in 1 patient because of a myocardial infarction. This trial confirms the inefficacy of rIL-2 for the treatment of large-cell NHL and HD. Conversely, in low-grade NHL, rIL-2 activity needs to be explored by further studies. rIL-2 may have a place in the early phase of the disease, when the immune system is not compromised, as an adjuvant treatment in residual disease in order to improve the duration of response.

The levels of c-myc protein expression in three types of Epstein-Barr virus (EBV) transformed human B-cell derived lines were examined with an ELISA assay. Six independently maintained sublines of the same EBV-transformed pro-B-cell line (FLEB-14), six B-cell lines (LCL) and six Burkitt's lymphoma lines (BL) were compared. The average amount of c-myc protein, calculated from at least three independent tests on each line, differed between the three groups. Expressed in relative units, the ratio of the means was 1:2:5 for the LCL:FLEB:BL lines. The differences were statistically significant at P < 0.01.

Adoptive immunotherapy with recombinant interleukin-2 (rhIL-2) has been reported to induce tumour regression in some patients with refractory cancer. However, the cardiovascular toxicity of bolus therapy requires invasive monitoring of patients in the intensive care unit (ICU). In an effort to examine the haemodynamic alterations caused by a constant infusion of IL-2, as opposed to bolus therapy, we studied the haemodynamic variables of 10 patients, with no evidence of heart disease, receiving 3 × 10⁶ IU/m² per day of rhIL-2 as a continuous infusion for 5 days. Measured and derived haemodynamic variables were obtained immediately prior to, at 2, 24, and 48 h during, and upon termination of the infusion. There was no evidence of clinical haemodynamic instability in these patients. Except for development of fever and tachycardia, there were no clinically significant differences in any measured or derived haemodynamic parameter. Moreover, continuous electrocardiographic monitoring of these patients during the infusion did not reveal any abnormalities. Invasive haemodynamic monitoring in an ICU is not necessary in carefully selected patients receiving constant infusion rhIL-2, at the described dose and schedule.

Several basic experimental and clinical studies were carried out in an attempt to improve the efficacy of alpha interferon therapy for chronic myelogenous leukaemia (CML). First, the combined use of hydroxyurea (HU) and interferon (500–1000 mg daily) in interferon-resistant cases facilitated maintenance of reduced leucocyte production, or a reduction in the dose of interferon, although suppression of Philadelphia chromosome (Ph¹)-positive clones was not observed in most cases. In order to try and decrease the rate of lymphoblastic crisis during the course of interferon therapy, we recently added methotrexate (MTX) (10–15 mg, weekly) to the treatment protocol. Since then, no lymphoblastic crisis has been observed. Second, the in vitro expression of alpha interferon-stimulated gene (ISG) mRNA was shown to be markedly decreased in granulocytes of one representative interferon-resistant case, compared to that in granulocytes of the three interferon-sensitive cases. Interestingly, it was found that the transcriptional activity in this case became almost normal when the blood granulocytes were controlled by the addition of HU. These findings suggest that the in vitro transcriptional assay of ISG mRNA may be clinically useful for predicting alpha interferon efficacy. Third, when genetically manipulated, alpha interferon-producing NIH/3T3 cells were co-transplanted using diffusion chambers into nude mice bearing a CML cell line, KU812, the CML tumour growth was shown to be markedly suppressed. This experimental model for alpha interferon replacement gene therapy suggests some directions for future studies on interferon therapy.

ras p21 expression, as indicated by the monoclonal antibody ras 11, was estimated using immunohistochemistry on 69 primary colorectal adenocarcinomas. Also, DNA ploidy and S-phase fraction (SPF) were analysed with flow cytometry. Positive staining for ras 11 tended to be more common in DNA non-diploid tumours (P = 0.11), but was significantly correlated with high SPF (P = 0.038). Positive ras 11 staining, Dukes' stage, DNA ploidy and SPF were related to the recurrence-free interval of patients with Dukes' A–C tumours (P = 0.0014, P = 0.023, P = 0.035 and P = 0.040, respectively). ras 11 staining was a prognostic factor independent of both Dukes' stage and DNA ploidy (P = 0.011). The results indicate that pan ras p21 expression is associated with proliferative activity and has an independent prognostic value in colorectal adenocarcinoma.