PURPOSE Tracheoesophageal fistulae are rare complications of thoracic cancers and their treatments. Novel antiangiogenic agents in cancer treatment such as bevacizumab potentially impact wound healing and may contribute to tracheoesophageal fistula development. PATIENTS AND METHODS We conducted two independent phase II clinical trials in small-cell lung cancer and non-small-cell lung cancer using bevacizumab in combination with chemotherapy and radiation. Both trials were intended to assess preliminary efficacy and safety outcomes. Results For the limited-stage small-cell lung cancer trial, 29 patients were enrolled beginning April 2006, and closed early due to toxicity in March 2007 (14-month median follow-up). The locally advanced, non-small-cell lung cancer trial opened with enrollment limited to five patients in February 2007, and closed early due to safety in December 2007. In each trial, we observed tracheoesophageal fistulae development and related morbidity and mortality, prompting early trial closures, US Food and Drug Administration warnings, and a change in bevacizumab labeling. CONCLUSION The current data from the final reports from these two trials suggest bevacizumab and chemoradiotherapy are associated with a relatively high incidence of tracheoesophageal fistulae formation in both small-cell lung cancer and non-small-cell lung cancer settings. Strategies to safely incorporate novel antiangiogenic agents into combined-modality therapy in lung cancer are needed.

We treated 22 patients with severe aplastic anaemia refractory to antithymocyte globulin (ATG) with cyclosporine, alone or in combination with prednisone. Eight patients showed significant clinical improvement, all but one to transfusion-independence. Although cyclosporine alone was effective, the addition of prednisone resulted in prompter and fuller haematologic improvement. No patient with an absolute granulocyte count less than 0.2 x 10(9)/l responded to treatment. Haematologic remissions were sustained beyond the treatment period. Of nine patients with Diamond-Blackfan syndrome, one showed a complete response to two separate courses of cyclosporine and relapse with withdrawal of therapy, and a second achieved significant reduction in corticosteroid dose without relapse; however, seven cases failed to respond. Two of three adults with acquired pure red cell aplasia recovered. A combination of cyclosporine and corticosteroids may be effective therapy in patients with aplastic anaemia who have failed ATG treatment. Occasional cases of congenital and acquired pure red cell aplasia may also respond to cyclosporine.

Summary:complete remission (CR) rates (40-50%) with median overall survivals of 18-24 months and progression-free survivals (PFS) of 12-25% in patients with breast cancer We investigated the outcomes of patients with breast cancer undergoing induction chemotherapy, mobilizresponsive to conventional induction chemotherapy. 1-6 A recent randomized phase III trial demonstrated the superioration of peripheral blood stem cells (PBSC) and highdose chemotherapy (HDC) with PBSC infusion. One ity of two cycles of HDC with peripheral blood stem cell (PBSC) support compared to conventional-dose treatment hundred and fourteen patients with untreated stage IV breast cancer, with a median age of 46 years (range 24-in patients with newly diagnosed metastatic breast cancer. 7Although HDC with PBSC support may be superior to 62), were entered on a phase II trial consisting of: (1) doxorubicin, 5-flurouracil, methotrexate (AFM) × 4 conventional-dose chemotherapy, the majority of patients will relapse and die of progressive disease or of attempts courses at 2 week intervals; (2) A phase II study was designed to enroll patients with stage IV breast cancer at diagnosis and to evaluate outThere was one infectious death after AFM and all other deaths were associated with progressive disease. Fiftycomes following the sequential administration of induction chemotherapy, chemotherapy and growth factor mobiliztwo patients (46%) are alive, 21 (18%) without progression, at a median 31 months (range 22-47). The ation of PBSC and HDC followed by PBSC infusion. Outcomes were analyzed and reported on an intent to treat basis probabilities of survival and progression-free survival at 3.5 years were 0.40 and 0.17, respectively. All 62 with a minimum follow-up of 24 months from enrollment. patients with visceral disease and/or a prior history of doxorubicin adjuvant therapy have relapsed or proPatients and methods gressed. We conclude that the sequential administration of AFM, CEP and CTCb followed by PBSC resulted in Between March 1992 and January 1994, 120 patients with untreated stage IV breast cancer were enrolled in a phase long-term PFS only in patients who were NED, had bone-only disease or had lymph node or soft tissue dis-II trial of chemotherapy induction, chemotherapy and filgrastim mobilization of PBSC, HDC and infusion of PBSC. ease with or without bone disease. Other strategies, aimed at improving responses to initial therapy, Patients were eligible if they had newly diagnosed and untreated breast cancer (except for adjuvant therapy), were improving HDC regimens and/or developing immunomodulatory therapies, will be necessary to improve PFS 65 years of age or less, had an ECOG performance of 0-1 and evidence of adequate hepatic, renal and cardiac funcfor patients who fail doxorubicin adjuvant or who have visceral disease.tion. Pre-menopausal women could be entered on the study without a previous trial of hormonal therapy. All patients Keywords: high-dose chemotherapy for breast cancer signed a protocol-specific informed consent appro...

BACKGROUND The purpose of the current study was to evaluate the efficacy and toxicity of the combination of fludarabine and rituximab, followed by alemtuzumab, as first‐line treatment for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). METHODS In a nonrandomized phase 2 trial, 41 patients who had previously untreated CLL or SLL and required treatment received 4 cycles of the fludarabine and rituximab combination followed 5 weeks later by 4 weeks (12 doses) of intravenous alemtuzumab therapy. The response to treatment was evaluated after completion of treatment with fludarabine and rituximab, and again after the completion of alemtuzumab consolidation. RESULTS Initial treatment with the combination of fludarabine and rituximab was well tolerated, and produced a 71% overall response rate (13% complete response). Thirty‐four patients began treatment with intravenous alemtuzumab, but this drug was relatively poorly tolerated when given at a short interval after fludarabine and rituximab, and only 20 patients (49% of total) were able to complete the prescribed course. Five patients had an improvement in their response with alemtuzumab; the final complete response rate was 21%. The median progression‐free survival for the entire group was 42 months. Toxicity with alemtuzumab included infusion‐related toxicity, myelosuppression, and opportunistic infections. CONCLUSIONS The intravenous schedule of alemtuzumab employed in the trial was relatively poorly tolerated in this community‐based trial. The relatively low complete response rates after treatment with the combination of fludarabine and rituximab and after the completion of treatment suggest that these abbreviated courses may compromise efficacy. The generalized use of alemtuzumab as consolidation therapy cannot yet be recommended for community practice. However, optimization of the route of administration, duration of treatment, and interval after completion of induction therapy may improve efficacy, and further investigation is ongoing. Cancer 2008. © 2008 American Cancer Society.