Multicenter phase II trial evaluating a three-weekly schedule of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer.

BACKGROUND: Irinotecan (CPT-11) and raltitrexed are active against advanced colorectal cancer (ACC), act through different mechanisms, and have only partially overlapping toxicity profiles. Phase I studies have shown that single-agent full doses of both drugs can be safely combined. The aim of this multicenter study was to assess the efficacy and toxicity of the combination in patients with 5-fluorouracil (5-FU)-refractory ACC. PATIENTS AND METHODS: Between October 1999 and December 2000, 52 patients (31 males, 21 females) with a median age of 62 years (range 39-75) were included and received CPT-11 (350 mg/m(2) as a 60-min infusion) plus raltitrexed (3 mg/m(2) as a 15-min infusion, 1 h after CPT-11), with courses repeated every 21 days. Objective response was assessed after every three courses, and treatment maintained until tumor progression or unacceptable toxicity. RESULTS: A total of 313 cycles were administered, with a median of six cycles per patient (range 1-14). Seven patients (13.5%) achieved a partial response and one a complete response (1.9%), for an overall intention-to-treat response rate of 15.4% (95% confidence interval 6.1% to 27.2%). The incidence of grade 3/4 toxicity was 23.1% for diarrhea, 21.2% for asthenia, 17.3% for neutropenia, 13.4% for emesis and 7.7% for infection. There were no treatment-related deaths. With a median follow-up of 20 months, median survival was 11.9 months and median time to progression was 4.6 months. CONCLUSIONS: CPT-11 plus raltitrexed is active in patients with 5-FU-refractory ACC, at the expense of moderate toxicity.

ESHAP is an active regimen for relapsing Hodgkin's disease.

BACKGROUND: Refractory or relapsing Hodgkin's disease is associated with a poor prognosis. There is no widely accepted salvage chemotherapy regimen for these patients. However, the addition of high-dose chemotherapy followed by autologous hematopoietic transplantation (AHT) has proven of benefit to them. A prospective clinical trial was carried out to evaluate the efficacy and toxicity of ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin). PATIENTS AND METHODS: Twenty-two patients with refractory (5) or relapsing Hodgkin's disease (17) were entered and scheduled to receive three courses of ESHAP. Patients suitable for AHT were then given high-dose chemotherapy with CBV (cyclophosphamide, carmustine, and etoposide) plus AHT, whereas responding, non-AHT-suitable patients completed six ESHAP courses. RESULTS: Nine patients achieved complete responses and seven partial responses (overall response rate 73%) with ESHAP. Grade 3-4 myelotoxicity was seen in 13 patients (59%). Nine patients received CBV plus AHT. At a median follow-up time of 50 months (range 6-96), seven patients (32%) are alive and disease-free. Three patients died of toxic effects of ESHAP (1) or CBV (2). Actuarial overall survival and disease-free survival were 35% and 27% at three years. CONCLUSIONS: ESHAP is an active regimen for relapsing Hodgkin's disease, with myelosuppression as its dose-limiting toxicity. An increased risk of treatment-related mortality when it is combined with high-dose chemotherapy can not be ruled out.

Long-term results after combined modality treatment for non-metastatic osteosarcoma.

Since the introduction of multimodality treatment, the prognosis of patients with high-grade non-metastatic osteosarcoma has significantly improved. A retrospective review was performed to assess the long-term results of this approach in a single centre setting, and to investigate the impact of potential clinical prognostic factors. Between 1985 and 1993, 35 patients with stage II-A and II-B osteosarcoma underwent preoperative chemotherapy (high-dose methotrexate), wide surgery, and adjuvant chemotherapy (cisplatin-doxorubicin/bleo-mycin-cyclophosphamide-dactinomycin) (modified T-10A protocol). There were 19 males and 16 females. Median patient age was 17 y (range 12-42). Primary tumour sites were the extremities (83%) and axial bones (17%). In spite of an unfavourable grade 3-4 histologic response rate to high-dose methotrexate of 12%, 31 (88%) patients were able to undergo limb-sparing surgery and 28 (80%) were rendered disease free after the planned therapy. Median follow-up was 8 y. The actuarial overall survival and disease-free survival rates were 64% and 49% at 5 y, and 59% and 49% at 10 y, respectively. Tumour size and primary site were significant prognostic factors for survival in univariate analyses. In conclusion, long-term survival after combined modality treatment can be achieved in more than 60% of patients with localised osteosarcoma, including non-appendicular lesions. Limb-sparing surgery is a realistic goal for most cases. The prognostic value of tumour necrosis and the efficacy of neoadjuvant chemotherapy should be interpreted according to individual high-dose methotrexate scheduling.