Hematopoetic stem cell transplantation for solid tumors in Europe.

BACKGROUND: Hematopoetic stem cell transplants (HSCT) are discussed as treatment options for patients with solid tumors. Transplant numbers have changed substantially over the last decade, few controlled studies are available and different opinions prevail. Objective information on current practice is needed. PATIENTS AND METHODS: Data from 27 902 HSCT for solid tumors (2% allogeneic, 98% autologous), collected by the European Group for Blood and Marrow Transplantation (EBMT) activity survey from 1991 to 2002 were used to assess trends, transplant rates and coefficient of variation of transplant rates in Europe. RESULTS: Transplant numbers increased from 536 in 1991 to 4154 in 1997 and decreased to 1913 in 2002. Indications were neuroblastoma (2504 HSCT; 9%), glioma (662 HSCT; 2%), soft tissue sarcoma (1253 HSCT; 4%), germ cell cancer (3291 HSCT; 12%), breast cancer (13 524 HSCT; 48%), Ewing's sarcoma (1896 HSCT; 7%), lung cancer (387 HSCT; 1%), ovarian cancer (845 HSCT; 3%) and other solid tumors (3540 HSCT; 14%). Allogeneic cells were used in <20 cases up to 1997; since then allogeneic HSCT increased to 159 in 2002, mainly for renal cell carcinoma. Low coefficients of variation in transplant rates (<60%) are observed for Ewing's sarcoma (<56.5%), suggesting consensus for this indication. CONCLUSIONS: These data give an overview on current practice of HSCT for solid tumors in Europe. They provide objective information for health-care providers and patient counselling.

Cyclophosphamide, methotrexate,5-fluorouracil, alternating with adriamycin and mitomycin C in metastatic breast cancer: a pilot study.

To explore the clinical applicability of the Goldie and Coldman hypothesis, we treated 28 patients with metastatic breast cancer with alternating non-cross-resistant chemotherapy. The patients received cyclophosphamide, 600 mg/m2, 5-fluorouracil, 600 mg/m2, methotrexate, 40 mg/m2, alternated every three weeks with adriamycin, 60 mg/m2, and mitomycin C, 10 mg/m2. Only one patient had previously received palliative chemotherapy. Six patients had received adjuvant CMF, and 17 patients had been pretreated with endocrine therapy (13 for advanced disease, 4 as adjuvant). Fourteen patients had bone involvement, and 10 had visceral metastases. A mean of 12 cycles was given to 24 evaluable patients. The objective response rate was 67%: 11 patients (46%) achieved complete and 5 (21%) partial remission. Response rate in soft tissues was 83.3%, in bone 50%, in liver 100%, and in lung 80%. The median duration of response was 14 months, with 7 patients still in remission. No life-threatening toxicity was observed. Our preliminary results support the validity of this approach and the efficacy of this combination chemotherapy. A large-scale randomized study is warranted.

Modulated chemo-hormonotherapy in advanced breast cancer. A pilot study.

Twenty-two patients with advanced breast cancer have been treated with sequential chemo-hormonotherapy consisting of tamoxifen 20 mg/day orally for 14 consecutive days, followed by no therapy for ten days, then estrogen 0.625 mg/day orally for three days; the next day methotrexate 200 mg/m2 i.v. and cyclophosphamide 600 mg/m2 i.v.; after 24 hours folinic acid 200 mg/m2 i.v. and 5-fluorouracil 600 mg/m2 i.v. Fifteen patients were evaluable for response, 22 were evaluable for toxicity. All but one were heavily pretreated with chemo and/or hormonotherapy. Nine of 15 had previously received palliative CMF (cyclophosphamide, methotrexate, 5-fluorouracil) (mean 9 cycles), and one patient 12 cycles adjuvant CMF. Thirteen of 15 previously received tamoxifen (median treatment of 18 months). Six patients had multiple metastatic disease, while five had visceral involvement. They were all postmenopausal, with median age 57 years, and median disease-free interval 31 months. ER status was not known and the median ECOG performance status was 1. Overall response rate was 20%. Only one patient attained complete remission; 46.6% were stable disease and 33.3% progressive disease. Accepting that the response rate is very low in pretreated patients, this 20% can be significant. Ninety cycles were administered to 22 patients and the treatment was very well tolerated: both hematologic and nonhematologic toxicities were mild.