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Phase II study of raltitrexed ('Tomudex') for patients with advanced soft tissue sarcomas refractory to
J Y Blay1, I Judson, S Rodenhuis
1EORTC Soft Tissue and Bone Sarcoma Group, Brussels, Belgium. blay@lyon.fnclcc.fr
Abstract:
Advanced soft tissue sarcomas (ASTS) refractory to therapy with doxorubicin and/or ifosfamide are highly resistant to therapy with other cytotoxic agents. The efficacy and safety of raltitrexed ('Tomudex') was assessed in patients with ASTS refractory to one or two doxorubicin- and/or ifosfamide-containing regimens in eight centers of the EORTC STBSG group. Raltitrexed was given at 3 mg/m2 as a 15 min i.v. infusion once every 3 weeks. Among the 23 patients [mean age 54 (range 25-73) years] included, 22 patients (15 males and seven females) were eligible and evaluable for response to therapy and 21 were evaluable for toxicity. Patients had previously received chemotherapy in metastatic phase (n=16), as adjuvant treatment (n=5) or both (n=1). The primary tumor was located in the trunk (n=11), in the limbs (n=8) or in the head and neck (n=3). Most patients (n=13) received two courses of raltitrexed (range 1-8). The best response was stable disease in five (23%) patients, while disease progression was noted in 17 patients (77%); the median time to disease progression was 6 weeks. The treatment was well tolerated with only one patient experiencing grade 4 neutropenia and thrombocytopenia, one patient experiencing grade 3 nausea, one lethargy, one headache, and one asthenia. Only one patient experienced febrile neutropenia. Raltitrexed as monotherapy is not an effective treatment for patients with ASTS who failed conventional chemotherapy with doxorubicin and ifosfamide.
Insights
Raltitrexed (Tomudex) showed limited efficacy in advanced soft tissue sarcomas (ASTS) resistant to doxorubicin or ifosfamide. The drug was generally well-tolerated but did not demonstrate significant anti-tumor activity in this refractory patient population.
Area of Science:
- Medical Oncology
- Pharmacology
- Cancer Research
Background:
- Advanced soft tissue sarcomas (ASTS) often develop resistance to conventional chemotherapy, including doxorubicin and ifosfamide.
- Identifying effective salvage therapies for refractory ASTS is a critical unmet need in cancer treatment.
Purpose of the Study:
- To evaluate the efficacy and safety of raltitrexed (Tomudex) as a monotherapy in patients with ASTS who have failed prior doxorubicin and/or ifosfamide-containing regimens.
- To assess the response rate, time to disease progression, and toxicity profile of raltitrexed in this heavily pre-treated patient cohort.
Main Methods:
- A phase II clinical trial involving 23 patients with refractory ASTS across eight centers.
- Raltitrexed was administered at a dose of 3 mg/m2 intravenously every 3 weeks.
- Patients were evaluated for response, disease progression, and treatment-related toxicities.
Main Results:
- Only 5 out of 22 evaluable patients (23%) achieved stable disease; 17 patients (77%) experienced disease progression.
- The median time to disease progression was 6 weeks.
- Raltitrexed was generally well-tolerated, with most adverse events being mild to moderate. Grade 4 neutropenia and thrombocytopenia occurred in one patient each.
Conclusions:
- Raltitrexed monotherapy is not an effective treatment for advanced soft tissue sarcomas that are refractory to conventional chemotherapy with doxorubicin and/or ifosfamide.
- Further investigation into combination therapies or alternative agents is warranted for this patient population.