Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD.

PURPOSE: The PETACC 6 trial investigates whether the addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative capecitabine improves disease-free survival (DFS) in locally advanced rectal cancer. METHODS: Between November 2008 and September 2011, patients with rectal adenocarcinoma within 12 cm from the anal verge, T3/4 and/or node positive, were randomly assigned to 5 weeks preoperative capecitabine-based chemoradiation (45-50.4 Gy) followed by six cycles of adjuvant capecitabine, both without (control arm, 1) or with (experimental arm, 2) oxaliplatin. The primary end point was improvement of 3-year DFS by oxaliplatin from 65% to 72% (hazard ratio [HR], 0.763). RESULTS: A total of 1,094 patients were randomly assigned (intention to treat), and 1,068 eligible patients started their allocated treatment (arm 1, 543; arm 2, 525), with completion of protocol treatment in 68% (arm 1) v 54% (arm 2). A higher rate of grade 3/4 adverse events was reported in the experimental arm (14.4% v 37.3% and 23.4% v 46.6% for neoadjuvant and adjuvant treatment, respectively). At a median follow-up of 68 months (interquartile range, 58-74 months), 157 and 156 DFS events were observed in arms 1 and 2, respectively (adjusted HR, 1.02; 95% CI, 0.82 to 1.28; P = .835). Three-year DFS rate was not different, with 76.5% (95% CI, 72.7% to 79.9%) in arm 1, which is higher than anticipated, and 75.8% (95% CI, 71.9% to 79.3%) in arm 2. The 7-year DFS and overall survival (OS) rates were not different as well, with DFS of 66.1% v 65.5% (HR, 1.02) and OS of 73.5% v 73.7% (HR, 1.19) in arms 1 and 2, respectively. Subgroup analyses revealed heterogeneity in treatment effect according to German versus non-German site location, without detectable confounding factors in multivariable analysis. CONCLUSION: The addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative adjuvant chemotherapy impairs tolerability and feasibility and does not improve efficacy.

Combined plasmapheresis and immunosuppression as rescue treatment of a patient with catastrophic antiphospholipid syndrome occurring despite anticoagulation: a case report.

We report the case of a 33-year-old female with known primary antiphospholipid syndrome who, despite full-dose oral anticoagulation, presented with myocardial infarction, acute respiratory distress syndrome, purulent bronchitis, and septic shock. Antiphospholipid antibodies and anti-beta2-glycoprotein-1 titres were markedly elevated. The patient was diagnosed with catastrophic antiphospholipid syndrome and treated with unfractionated intravenous heparin. However, she developed thromboembolism of the right foot and skin marmoration of her extremities during heparin therapy, and therefore plasmapheresis, immunoglobulins, cyclophosphamide, and methylprednisone under a broad spectrum of anti-infective therapy were instituted. This treatment led to a rapid decrease of antiphospholipid antibody and anti-beta2-glycoprotein-1 titres, and the patient's condition gradually improved. Upon discharge from the hospital, pulmonary infiltrates had markedly regressed, and she was feeling well. Given the high mortality of catastrophic antiphospholipid syndrome, this report emphasizes the need for rapid diagnosis and effective multimodal treatment in an intensive care unit setting for these patients.

Effective treatment of simultaneous small cell lung cancer and B-cell lymphoma.

Malignant lymphomas have been reported previously to coincide with adenocarcinomas of the stomach and, rarely, the kidney, breast, colon, liver, or lung. Here, we describe the first case to our knowledge of a malignant lymphoma and an extensive disease small cell cancer of the lung. A 60-year-old male was admitted for severe back pain and was found to have multiple enlarged lymph nodes, hepatosplenomegaly, and bilateral pleural effusions. A B-cell non-Hodgkin's lymphoma (NHL) was diagnosed from biopsies of the stomach and liver. Further staging revealed a dense infiltration of the bone marrow by both a small cell lung cancer and a malignant lymphoma. Both tumors responded well to chemotherapy. This unique case report demonstrates that the simultaneous occurrence of small cell lung cancers and malignant lymphomas is extremely rare and may effectively be treated with chemotherapy.

Induction of apoptosis by cladribine (2-CdA), gemcitabine and other chemotherapeutic drugs on CD34+/CD38+ and CD34+/CD38- hematopoietic progenitor cells: selective effects of doxorubicin and 2-CdA with protection of immature cells.

Due to the emerging role of high dose chemotherapy with stem cell rescue and ex vivo purging in hematological diseases, we examined the effect of chemotherapeutic drugs on the rate of apoptosis in more mature CD34+/CD38+ and less differentiated CD34+/CD38- stem cells. CD34+ cells were obtained by cell apheresis from healthy donors (n = 25) or patients (n = 25) prepared for high dose chemotherapy and stem cell transplantation. Cells were incubated with different concentrations of doxorubicin, mitoxantrone, mafosphamide, cladribine or gemcitabine. Apoptosis was determined after 24 and 48 h. Generally, the percentage of apoptotic cells was higher in the more mature CD34+/CD38+ progenitor population than in the less differentiated CD34+/CD38- cells. By analysis of variance (ANOVA) significantly (p < 0.05) more apoptotic cells within the CD34+/CD38+ progenitors were calculated after incubation with mafosphamide, doxorubicine and cladribine. Mafosphamide induced the highest rate of apoptosis on CD34+/CD38- cells, whereas doxorubicine had nearly no effect on this immature population. Dose effect plots for mafosphamide and doxorubicin were steep, suggesting a large therapeutic index. The dose response of cladribine showed a flat course. Furthermore we found a selective induction of apoptosis by doxorubicin and cladribine on more mature CD34+/CD38+ progenitors in contrast to simultaneous protection of CD34+/CD38- progenitors. From these findings, in particular the demonstrated low stem cell toxicity, we conclude that doxorubicin and cladribine might be efficient alternatives in ex vivo purging of autologous grafts, as well as safe components in primary treatment schedules of lymphomas or prior to stem cell harvest with respect to stem cell toxicity.