Norbert Niederle

Efficacy and toxicity of bendamustine in patients with relapsed low-grade non-Hodgkin's lymphomas.

Low-grade non-Hodgkins lymphomas (NHL) are very sensitive to a broad range of chemotherapeutic and biological agents. Relapses, however, occur even after aggressive cytostatic combinations in first-line therapy. Therefore, effective and well-tolerated salvage therapies are very important. In this single-institution trial, the efficacy and toxicity of bendamustine in the treatment of relapsed low-grade NHL was investigated. Fifty-eight patients with low-grade NHL pretreated with different cytostatic regimens were included. All patients received bendamustine at 120 mg/m2 as a 1-h infusion on 2 consecutive days. The treatment was repeated every 3 weeks until complete remission (CR), partial remission (PR) or stable disease (SD) was confirmed on two consecutive cycles. Efficacy and toxicity were evaluated in 52 patients: CR was induced in 11%, PR in 62% and SD in another 10% of the patients. No response to treatment was seen in 17%. The median duration of remission was 16 months and the median survival time was 36 months. Side effects were generally mild, and restricted to myelosuppression, gastrointestinal toxicity and allergic reactions. Bendamustine proved to be very effective and was well tolerated in pretreated patients with relapsed or primary resistant low-grade NHL.

Hypersensitivity reactions to carboplatin. Report of two patients, review of the literature, and discussion of diagnostic procedures and management.

Background. Hypersensitivity reactions are rare but sometimes life‐threatening complications of cytostatic combinations containing platinum compounds. Only approximately 40 instances of such hypersensitivity have been reported in association with carboplatin treatment. However, the symptoms probably often are misinterpreted.

Efficacy of ifosfamide in refractory malignant diseases and uroprotection by mesna: results of a clinical phase II-study with 151 patients

In a clinical phase II study 151 patients with refractory malignant diseases were treated with ifosfamide (60 mg/kg/day i.v. days 1-5, q 21-28 days). Altogether, 490 courses of treatment were given, 92 with conventional prophylactic measures (continuous infusion of 3-4 litre physiological saline plus alkalinization of the urine) and 398 with mesna prophylaxis (12 mg/kg i.v., 0, 4 and 8 h after administration of ifosfamide). The overall response rate (min. 25% tumor reduction) was 67/151 (44%) including four complete remissions in a fairly unfavourable patient group with testicular teratoma (39/87), soft tissue sarcoma (10/16), malignant melanoma (2/7), osteogenic sarcoma (3/6), Ewings sarcoma (2/6), lymphoma and acute leukemia (5/7) or other histologies (6/22). The response rate in patients pretreated by cyclophosphamide containing regimen was 7/19 (36%) including one complete remission and one partial remission. Mesna was highly effective in reducing the frequency of hemorrhagic cystitis from 25/92 (27%) to 16/398 (4%) ifosfamide courses. The antitumor activity of ifosfamide in testicular cancer was not reduced by mesna. In conclusion, ifosfamide with the potent uroprotector mesna appears to compare favourably with the most active agents in the treatment of malignant diseases.

Advanced male breast cancer treatment with the LH-RH analogue buserelin alone or in combination with the antiandrogen flutamide

Ten men with advanced breast cancer were evaluated for response to treatment with the luteinizing hormone‐releasing hormone (LH‐RH) analogue, buserelin, alone or in combination with the antiandrogen, flutamide. One of five patients receiving buserelin as a single agent had a partial remission lasting 12 months, and with the addition of flutamide, this lasted over 24 additional months. Three patients had stable disease with a median duration of 6 months (range, two to 14). One patient had progressive disease. Of five patients receiving the combination of buserelin and flutamide from the beginning of therapy, four patients had a partial remission with a median duration of over 15 months (range, over five to 16). One patients disease remained stable for 12 months. Major side effects were hot flushes, loss of libido, and impotence. Buserelin initiates a castration‐like endocrine response and has potential in the treatment of men with disseminated breast cancer when used either alone or in combination with flutamide.

5-Fluorouracil cardiotoxicity with left ventricular dysfunction under different dosing regimens

Abstract The observations reported here support the hypothesis that 5-FU induces a reversible cardiopathy (having a common final pathway with ischemia), including myocardial dysfunction, with a potentially fatal course. Although a clear dose-response relation is not evident, the incidence seems to be increased with recently promoted 24-hour high-dose 5-FU/ folinic acid combination therapy. There may be a cumulative “threshold dose” of 1,500 to 7,000 mg. To date, predisposing factors as well as a reliable treatment and prophylaxis are not well defined.

Etoposide and etoposide-ifosfamide therapy for refractory testicular tumors.

Summary A total of 165 patients from the West German Tumor Center in Essen suffering from a malignant testicular tumor received treatment with etoposide alone or in combination. Since this was adjuvant therapy and no measurable tumor parameters were available at the time of etoposide administration in 92 patients, the efficacy of etoposide treatment could be analysed retrospectively in only 73 patients. Thirty-seven of these patients received treatment with etoposide alone (dosage usually 120 mg/m 2 p.o. days 1–5 every 4 weeks) and 36 received treatment with a combination of etoposide and ifosfamide (dosage: etoposide 120 mg/m 2 i.v. days 1, 3, 5 and ifosfamide 40 mg/kg i.v. days 1, 5 every 3–4 weeks) when prior treatment with cytostatics had not been able to achieve complete remission, or the tumors had recurred. In patients treated with etoposide alone a total response rate of 24.3% was observed. In contrast, remission of the tumor was achieved in 58.3% of the patients receiving the etoposide-ifosfamide combination. Despite prior comprehensive cytostatic treatment, etoposide was still effective in some patients with refractory malignant testicular tumors. This was especially true of the etoposide-ifosfamide combination, as ifosfamide showed little cross-resistance with the previously administered cytostatics.

Hypersensitivity reactions to parenteral lipid solutions

Abstractu2002In cancer patients, hypersensitivity reactions to adjunctive medications are easily mistaken for cytostatic toxicities. We report on three patients with systemic reactions (flush, dyspnea, tachycardia, hypotension, back pain) to a lipid emulsion containing long chain fatty acids (LCT). Reexposure to LCT and exposure to MCT (medium chain fatty acids) solutions of slightly different composition – no soybean lecithin used as an emulsifier – were well tolerated. These data suggest that traces of soybean proteins are the allergenic agents. Therefore, hypersensitivity to concomitant medications, including parenteral nutrition, has to be considered in oncologic patients demonstrating severe systemic reactions to intravenous therapy.

Ifosfamide in combination chemotherapy for sarcomas and testicular carcinomas.

The efficacy of ifosfamide combination chemotherapy was studied in 164 patients, 94 with advanced testicular carcinoma and 70 with metastatic sarcoma. Ifosfamide was given at 40-60 mg/kg/day i.v. on five consecutive days every 3-4 weeks together with mesna prophylaxis with 8 mg/kg i.v. being used at 0, 4 and 8 h after ifosfamide administration. Of 70 sarcoma patients 57 were evaluable for response, of whom 49 had received prior chemotherapy. The overall response rate was 46% (26/57) including 3 complete (CR) and 14 partial remissions (PR). Ninety-four patients with germ cell tumours of the testis were treated. Of 16 seminoma patients 15 achieved CR or PR. Seventy-eight patients with nonseminomatous testicular cancer who had received previous chemotherapy were either treated with ifosfamide/etoposide (n = 63, remission rate: 30%) or ifosfamide/cisplatin (n = 15, CR + PR: 33%). These results indicate that ifosfamide alone or in combination is active in sarcomas, seminomas and teratomas and that further studies are warranted employing the drug in first-line regimens.

Phase II Trial with Carboplatin and Bendamustine in Patients with Extensive Stage Small-Cell Lung Cancer

Background: Bendamustine is an alkylating agent with hybrid activity and proven efficacy in small-cell lung cancer associated with a favorable toxicity rate. This phase II study of carboplatin/bendamustine was conducted to evaluate the efficacy of this combination in patients with extensive disease small-cell lung cancer (ED-SCLC). Methods: Fifty-six untreated patients with ED-SCLC were enrolled. Their median age was 63 years. Sixty-seven percent of patients were male and 18% had a World Health Organization performance status of 2. Bendamustine was administered as a 30- to 60-minute infusion at a dose of 80 mg/m2 on days 1 and 2, and carboplatin was given at an area under the curve of 5 on day 1 of a 21-day cycle. Results: Fifty-five patients were assessable for response and toxicity. The overall response rate was 72.7% (95% confidence interval: 59%–84%), with one complete remission (1.8%). The median time to progression was 5.2 months (95% confidence interval: 4.2–5.6). At the time of evaluation, 71% of the patients had died. The median survival time reached 8.3 months (95% confidence interval: 6.6–9.9). The major toxicity of this regimen was myelosuppression, including grade 3 or 4 neutropenia (46%), thrombopenia (26%), anemia (15%), and infections (11%). Toxic death was recorded in two patients (3.6%). Conclusions: The carboplatin/bendamustine regimen is a well-tolerated cytostatic combination in ED-SCLC with activity comparable with that of other platinum-based regimens. Further investigations, such as a phase III trial, are currently planned.

Treatment of chronic myelogenous leukemia with recombinant interferon alfa-2b

SummaryInterferon alfa-2b (Intron A; Schering-Plough) was administered to 36 patients with chronic myeloid leukemia (CML) at an initial dose of 4 × 106 IU/m2 daily subcutaneously, adapted to changes in leukocyte counts during the course of treatment. Of 32 patients who could be fully evaluated (20 men and 12 women; median age, 34 years) 29 were in the chronic phase, one had a blast crisis and two had accelerated phase disease.Hematologic remission was achieved in 20 of the 32 patients, while a partial hematologic remission was obtained in 10. Elevated pretreatment white-cell counts returned to normal in 25 patients after 3–40 weeks. There was a parallel decrease in platelet counts after an average treatment time of six weeks and in lactate dehydrogenase, after 2–20 weeks. In conclusion, administration of interferon alfa-2b resulted in a relatively rapid cell reduction in chronic phase CML. The long-term effect of this treatment on the course of the disease and the place of interferon alfa-2b in the overall concept of CML treatment remains to be evaluated.