Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.

PURPOSE: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles. RESULTS: Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. CONCLUSION: Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.     

Chemotherapy induces the expression of cyclooxygenase-2 in non-small cell lung cancer.

PURPOSE: To determine the effect of taxane-based chemotherapy on intratumoral levels of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Lung specimens obtained at the time of surgery were used to measure levels of COX-2 and PGE(2) in tumors and adjacent nontumorous tissues in three subsets of NSCLC patients who underwent: (A) surgical resection only (n = 16); (B) surgical resection after preoperative taxane-based chemotherapy (n = 13); or (C) surgical resection after preoperative chemotherapy coadministered with the selective COX-2 inhibitor, celecoxib 400 mg bid (n = 17). RESULTS: Levels of intratumoral PGE(2) were nearly 3-fold higher among patients who received preoperative chemotherapy compared with those treated by surgery alone (P < 0.001). This difference was abrogated by the addition of celecoxib to preoperative chemotherapy (P < 0.001). Amounts of intratumoral COX-2 were approximately 3-fold higher in groups of patients who received preoperative chemotherapy with celecoxib (P < 0.0001) or without celecoxib (P < 0.001), compared with the group who underwent surgical resection only. Importantly, statistically significant positive correlations between COX-2 and PGE(2) were observed in the surgery only (r = 0.502, P = 0.047) and preoperative chemotherapy groups (r = 0.740, P = 0.004); this correlation was abrogated when celecoxib was given with chemotherapy (r = 0.005, P = 0.98). CONCLUSIONS: Treatment with chemotherapy led to increased amounts of COX-2 and PGE(2) in NSCLC. Cotreatment with celecoxib abrogated the increase in levels of PGE(2) but not COX-2 induced by chemotherapy. Importantly, these results clearly show that levels of a pharmacologic target (i.e., COX-2) can be affected by both the intrinsic molecular properties of a tumor and therapy.     

Radioquimioterapia de la enfermedad limitada del carcinoma pulmonar de célula pequeña. ¿Tratamiento concomitante en protocolos asistenciales?

Purpose We retrospectively reviewed our institution’s database to investigate the outcome and impact of combined radiochemotherapy (RT/CT; concomitant or in sequence) in localised small-cell lung cancer (L-SCLC). Material and methods Between January 1995 to November 1999, 79 patients with L-SCLC received combined RT/CT at our Institution. RT was delivered concurrently or sequentially following the CT. Patients with treatment response received additional prophylactic cranial irradiation (PCI). Results Of the patients treated, 54% had received concurrent CT/RT compared to 46% receiving RT following the CT. PCI was administered to 80% of the patients. Complete response was observed in 66% of patients. With a median follow up of 30 months, median overall survival was 15.9 months; 14.3 months for patients who received RT following CT and 21.6 months for those receiving concurrent CT/RT. The type of schedule of combined radiochemotherapy was an independent prognostic factor for survival free of local recurrence, as was additional PCI for distant metastasis-free survival. Conclusions Our results are similar to those reported previously in the literature. The main point of interest is that our patients were non-selected. We strongly support the use of concurrent CT/RT so as to achieve results comparable to the best in the literature.

     

Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma.

PURPOSE: Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.5 mg/m2) on days 1, 4, 8, and 11 every 21 days for a maximum of six cycles. RESULTS: Sixty patients with a median number of prior therapies of 3.5 (range, one to 12 therapies) were enrolled; 33 patients were in arm A and 27 were in arm B, including 12 diffuse large B-cell lymphomas, five follicular lymphomas (FL), three transformed FLs, four small lymphocytic lymphomas (SLL), two Waldenstrom's macroglobulinemias (WM), and one marginal zone lymphoma. In arm A, 12 of 29 assessable patients responded (six complete responses [CR] and six partial responses [PR]) for an overall response rate (ORR) of 41% (95% CI, 24% to 61%), and a median time to progression not reached yet, with a median follow-up of 9.3 months (range, 1.7 to 24 months). In arm B, four of 21 assessable patients responded (one SLL patient had a CR, one FL patient had a CR unconfirmed, one diffuse large B-cell lymphoma patient had a PR, and one WM patient had a PR) for an ORR of 19% (95% CI, 5% to 42%). Grade 3 toxicity included thrombocytopenia (47%), gastrointestinal (20%), fatigue (13%), neutropenia (10%), and peripheral neuropathy (5%). Grade 4 toxicity occurred in nine patients (15%), and three deaths from progression of disease occurred within 30 days of withdrawal from study. CONCLUSION: Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas. Future studies will explore bortezomib in combination with other cytotoxic or biologic agents.     

Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer.

PURPOSE: Cancer-testis genes mapping to the X chromosome have common expression patterns and show similar responses to modulators of epigenetic mechanisms. We asked whether cancer-testis gene expression occurred coordinately, and whether it correlated with variables of disease and clinical outcome of non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Tumors from 523 NSCLC patients undergoing surgery were evaluated for the expression of nine cancer-testis genes (NY-ESO-1, LAGE-1, MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, CT7/MAGE-C1, SSX2, and SSX4) by semiquantitative PCR. Clinical data available for 447 patients were used to correlate cancer-testis expression to variables of disease and clinical outcome. RESULTS: At least one cancer-testis gene was expressed by 90% of squamous carcinoma, 62% of bronchioloalveolar cancer, and 67% of adenocarcinoma samples. Statistically significant coexpression was observed for 34 of the 36 possible cancer-testis combinations. Cancer-testis gene expression, either cumulatively or individually, showed significant associations with male sex, smoking history, advanced tumor, nodal and pathologic stages, pleural invasion, and the absence of ground glass opacity. Cox regression analysis revealed the expression of NY-ESO-1 and MAGE-A3 as markers of poor prognosis, independent of confounding variables for adenocarcinoma of the lung. CONCLUSIONS: Cancer-testis genes are coordinately expressed in NSCLC, and their expression is associated with advanced disease and poor outcome.     

Viral infections and implications for male reproductive health

Viral infections have haunted humankind since times immemorial.Overpopulation,globalization,and extensive deforestation have created an ideal environment for a ...     

Evolution of the retinal function by flash-ERG in one child suffering from neuronal ceroid lipofuscinosis CLN2 treated with cerliponase alpha: case report

Documenta Ophthalmologica - Neuronal ceroid lipofuscinoses (CLN) are neurodegenerative disorders among the most frequent, inherited as an autosomal recessive trait. Affected patients can present...     

Tracheal and laryngotracheal resections and reconstructions—a single-centre experience

BackgroundSurgical resection has proven to be the most effective long-term treatment in managing airway stenoses and has shown to decrease the risk of tumor recurrence and mortality in patients with tumor infiltration to the airways. However, there are only a few Nordic reports on the results of a tracheal resection (TR) and cricotracheal resection (CTR). This study aimed to evaluate the volume and short-term outcome of TR and CTR at our institution.MethodsRetrospective review of patients who underwent TR or CTR between 2004 and 2019 at the Helsinki University Hospital (Helsinki, Finland).ResultsForty-four patients were included, of which 21 (47.7%) underwent surgery for a tumor, whereas 23 (52.3%) were operated for a benign stenosis. The most common tumor type was thyroid carcinoma with tracheal invasion (15.9%). The distance between the upper margin of the stenosis or tumor infiltration and the vocal cords was in median 3 [interquartile range (IQR), 2–5] cm and the median length of resection 2.5 (IQR, 2–3.5) cm. Overall success rate was 75% (no need for reoperation or postoperative intervention). Complications occurred in 20 (45.5%) patients, of which 10 patients were operated for a tumor, and 10 for a benign stenosis.ConclusionsTracheal and CTRs were effective in treating tracheal and subglottic stenoses with variable etiology. However, complications were common especially following cricotracheal tumor resections. These procedures show a clear need for further centralization due to their complex nature and should therefore be performed primarily at institutes with highly experienced multi-professional teams.