Salvage chemotherapy for metastatic breast cancer: results of a phase II study with bendamustine.

BACKGROUND: Bendamustine, a bifunctional alkylating agent with anticipated purin-like properties is active in metastatic breast cancer (MBC) patients. This multicenter phase II trial defines the toxicity and activity of bendamustine in heavily pretreated patients. PATIENTS AND METHODS: Fifty-one patients were included. Patients had a median number of 2 prior chemotherapeutic regimens for MBC (range 0-7) consisting of anthracyclines and taxanes: 26 patients (51%); anthracyclines: nine patients (17.6%); taxanes: seven patients (13.7%); others: five patients (9.8%). Bendamustine was administered four weekly at a dose of 120 mg/m(2) on days 1 and 2. RESULTS: Fifty patients were assessable. Of total, 200 courses were administered. We observed no complete response (CR); 10 patients [20%; 95% confidence interval (CI): 10.0% to 33.7%] achieved a partial response (PR), 14 patients (28%) remained stable for at least 6 months resulting in a clinical benefit rate (CR + PR + stable disease) of 48% (95% CI: 33.7%to 52.6%). Median time to progression was 3.4 months (range 1-51.1). The median duration of remission was 6.6 months (range 1.8-48.7). The treatment was well tolerated with mainly hematologic toxic effects. CONCLUSION: Single-agent bendamustine is an active treatment in patients with MBC independent of the previous treatment. The low toxicity profile favors its use as a single agent.

Treatment of advanced rectal cancer in a patient after combined pancreas-kidney transplantation.

BACKGROUND: Organ transplantation is a standard procedure today. Due to immunosuppressive drugs and increasing survival after organ transplantation, patients with transplanted organs carry an increased risk of developing malignant tumours. Accordingly, more patients with malignant tumours after transplantation will be faced by general or oncology surgeons. We report the case of a 48-year-old patient with advanced rectal cancer 6.5 years after pancreas-kidney-transplantation for type I diabetes. METHOD: The patient was treated with neo-adjuvant radio-chemotherapy, followed by low anterior rectal resection with total mesorectal excision. Consecutively, a solitary hepatic metastasis, a solitary pulmonary metastasis and a chest wall metastasis were resected over the course of 13 months. RESULT: The patient eventually died of metastasized cancer 32 months after therapy had been initiated, his organ grafts functioning well until his death. CONCLUSION: Our case report provides evidence that transplantation patients should receive standard oncology treatment, including neo-adjuvant treatment, so long as their general condition and organ graft functions allow us to do so, although a higher degree of morbidity might be encountered.

Time- and dose-limiting erysipeloid rash confined to areas of lymphedema following treatment with gemcitabine--a report of three cases.

Gemcitabine is a deoxycytidine analog with broad antitumor activity. Its main toxicities include myelosuppression, flu-like symptoms, bronchospasms and mild skin rash. We report three cases, in which the patients developed time- and dose-limiting erysipeloid skin reactions confined to areas of impaired lymphatic drainage after application of gemcitabine. Three patients with metastatic tumors (breast cancer, endometrial cancer and non-small cell lung cancer) received weekly infusions of gemcitabine (1000 mg/m2). All patients suffered from lymphedema of different origin and developed an erysipeloid erythema 40-48 h after chemotherapy within their preexisting lymphedema. Genuine erysipela was ruled out by laboratory tests and clinical observation. The skin reaction was repeatedly observed and faded after 14 days without specific treatment. Although the pathogenesis of the observed reaction is unclear, it is suspected that the skin symptoms were caused by gemcitabine or its metabolites. Gemcitabine is usually metabolized fast and excreted renally. In areas with impaired lymphatic drainage pharmakocinetics might be altered: inactivation happens slower and the drug might accumulate in the s.c. and cutaneous tissue, thus increasing local toxicity. Clinical judgement and biochemical parameters can help to tell apart genuine erysipela and the erysipeloid reaction.

Recombinant interferon alpha 2 stimulation of target-binding by natural killer cells.

Even though the enhancement of the lyitc capacity and the kinetics of lysis of natural killer cells (NK) by interferon has been well documented, an increase of the target-effector cell binding percentage is still disputed. We, therefore, modified the Grimm-Bonavida single-cell assay so that 400 to 600 cells per individual determination could be reliably evaluated. Using this assay, which makes possible separate determination of effector-target cell binding and target lysis, we demonstrated that, in addition to lytic capacity, target-effector cell binding is also increased by preincubating NK with 100 to 1,000 IU interferon alpha 2 per 10(6) cells. Our data indicate that interferon alpha 2 induces pre-NK cells to bind target cells and that it activates these pre-NK cells to kill the targets.

Effect of human fibroblast interferon on natural killer cell activity: stimulation in vitro and inhibition in vivo.

This paper describes the influence of human fibroblast interferon (IFN-beta) on the cytotoxic activity of natural killer cells (NK) in vitro and in vivo using the blood of healthy donors and myeloma patients. IFN-beta stimulates NK activity against all target cells tested in vitro in a dose-dependent way up to 250% of pretreatment values. At higher IFN concentrations, stimulation returned to baseline values. Stimulation was most pronounced in the lowest lymphocyte to target cell ratio. 1- to 2-h preincubation of effector cells with IFN was enough to achieve maximal stimulation. The effector cells of IFN-treated myeloma-patients, or patients with herpes zoster, showed a clear reduction of toxicity against all cells tested during the first infusion, as compared to the pretreatment values.