Treatment of older patients with mantle-cell lymphoma.

BACKGROUND: The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether maintenance therapy with rituximab prolonged remission. METHODS: We randomly assigned patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to maintenance therapy with rituximab or interferon alfa, each given until progression. RESULTS: Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects occurred more frequently in the R-FC group than in the R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall survival (4-year survival rate, 87%, vs. 63% with interferon alfa; P=0.005). CONCLUSIONS: R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphoma. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT00209209.).

Initial chemotherapy with mitoxantrone, chlorambucil, prednisone impairs the collection of stem cells in patients with indolent lymphomas--results of a randomized comparison by the German Low-Grade Lymphoma Study Group.

Myeloablative radio-chemotherapy with subsequent autologous stem cell transplantation (ASCT) significantly prolongs progression free and probably overall survival in follicular lymphoma (FL) in first remission. The current trial explored prospectively the rate of successful stem cell mobilization in patients with advanced stage FL after initial therapy with either Mitoxantrone, Chlorambucil, Prednisone (MCP) or Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) as part of a prospective randomized comparison of both regimens. ASCT patients received Dexa-BEAM (Dexamethasone, BCNU, Melphalan, Etoposide, Cytarabine) for mobilization of stem cells. Stem cells were collected and a minimum of 2x2.0x106/kg bw CD34+ was required for ASCT. Of 79 evaluable patients, 58 (73%) had follicular lymphoma, 13 (16%) mantle cell lymphoma and 8 (10%) lymphoplasmacytic lymphoma. In the 45 patients assigned to CHOP, stem cell collection was successful in 42 cases (93%, 95% CI 82% to 99%). This high mobilization rate after CHOP could be confirmed in 61 subsequent patients (87%). In contrast, after MCP therapy stem cell collection was successful in only 15 of 34 patients (44%, 95% CI 27% to 62%; P=0.0003). In conclusion, initial therapy with MCP significantly impairs the ability to collect stem cells and should be avoided for first line therapy of younger patients potentially qualifying for high dose consolidation and ASCT in first remission.

[Increased response rate with rituximab in relapsed and refractory follicular and mantle cell lymphomas -- results of a prospective randomized study of the German Low-Grade Lymphoma Study Group]. / Rituximab zur Remissionsinduktion bei rezidivierten und refraktären indolenten Lymphomen und Mantelzell-Lymphomen - Ergebnisse einer prospektiv randomisierten Studie der deutschen Studiengruppe für niedrig maligne Lymphome (GLSG) -

BACKGROUND AND OBJECTIVE: Rituximab has shown a high activity in relapsed follicular lymphomas when given alone. Further on, phase-II-studies indicate that its addition to chemotherapy may improve the response rate substantially. However, so far, prospective randomized studies have not been available. PATIENTS AND METHODS: In 1998 the GLSG started a multicenter trial in patients with relapsed or refractory indolent lymphoma or mantle cell lymphoma. A fludarabine-containing regimen (FCM) was chosen for salvage therapy, with fludarabine 25 mg/m(2)/d 1-3, cyclophosphamide 200 mg/m(2) d 1-3 and mitoxantrone 8 mg/m(2) d 1. A total of four courses, every 4 weeks were given. Patients were prospectively randomized for FCM alone or the immunochemotherapy with R-FCM (375 mg/m(2) one day before FCM) RESULTS: About 147 randomized patients 93 had follicular, 40 mantle cell and 14 lymphoplasmocytic/-cytoid lymphoma. Statistical analysis was performed by sequential testing and indicated for 94 fully evaluable patients a significant advantage for the R-FCM-arm, with an overall response rate of 83 % as compared to 58%, when treated with FCM alone (CR: 35 % vs. 13 %). Similar improvements of remission rate were detected in the different lymphoma subgroups, especially in MCL (OR: 65 % vs. 33 %). Both treatment options were associated with hematological toxicities of grade III and IV, but well tolerated; infectious complications were rare, with no difference between the two treatment groups. CONCLUSION: This prospectively randomized trial demonstrates for the first time a significant improvement of the combined immunochemotherapy related to the remission rate in patients with relapsed or refractory indolent lymphoma.

Weekly docetaxel (Taxotere) in patients with metastatic breast cancer.

BACKGROUND: Docetaxel (Taxotere) has demonstrated high antitumour activity in first- and second-line treatment of metastatic breast cancer. This study analysed the efficacy and toxicity of docetaxel given weekly. PATIENTS AND METHODS: Thirty-five patients with metastatic breast cancer received docetaxel, 35 mg/m2 weekly for six weeks, followed by two weeks without treatment. Additional cycles (three weeks' treatment, two weeks' rest) were given until disease progression. All patients had received prior chemotherapy: 32 and 5 patients had received prior anthracycline-containing and taxane-containing regimens, respectively. Docetaxel was administered for a total of 359 doses (median 9. range 6-22). RESULTS: There was one complete response (3%), 11 partial responses (31%), 17 patients with stable disease (49%) and six with disease progression (17%). Overall response rate was 34% (95% confidential interval (95% CI): 18%-51). Median survival was 307 days; median progression-free survival was 2.6 months (range 1.5 to > or = 5.5 months). Three patients showed grade 3 neutropenia. 14 showed grade 3 alopecia, and various grade 1-2 non-haematological toxicities were observed. Treatment was delayed in two patients due to haematotoxicity. and stopped in one patient due to painful nail toxicity. CONCLUSION: Weekly administration of docetaxel at a dose of 35 mg/m2 is effective and of low toxicity in patients with metastatic breast cancer.

Metastases to the breast from rhabdomyosarcoma: appearances on MRI.

The authors report a case of blood-borne bilateral metastatic breast disease of alveolar rhabdomyosarcoma (RMS) in a 21-year-old patient. The possibilities of mammography, ultrasound, and MRI in the early detection of breast metastases and their appearance on these modalities are discussed. Whereas mammography rendered no additional information due to dense breast parenchyma and ultrasound showed only a solitary tumor without definite criteria of malignancy, multifocal bilateral spread was verified with MRI and early ring-like enhancement suggested malignancy. Therefore, we conclude that MRI may provide useful information in evaluating patients with sarcomas, even when there is no clinical evidence for metastatic disease of the breast.