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Phase II trial of gemcitabine in patients with pretreated advanced soft tissue sarcomas
E Späth-Schwalbe1, I Genvresse, A Koschuth
1Charité, Department of Oncology/Hematology, Humboldt University, Berlin, Germany. ernst.spaeth-schwalbe@charite.de
Abstract:
Because of the low number of active cytotoxic drugs and their limited activity, the evaluation of new anti-cancer agents for their activity in soft tissue sarcomas is a continuing need. The objectives of this prospective phase II trial of gemcitabine were to estimate the response rate and to define the toxicities of prolonged infusions of low-dose gemcitabine in patients with pretreated advanced soft tissue sarcomas. Patients were eligible if they had a histologic diagnosis of unresectable, recurrent or metastatic, progressive soft tissue sarcoma, and if they had been treated with at least one prior chemotherapy consisting of an anthracycline- and/or ifosfamide-containing regimen. Gemcitabine was administered as a 360 min infusion on days 1, 8 and 15 of a 28 day cycle. The initial dose of gemcitabine was 200 mg/m2 in all patients. Dose escalation to 250 mg/m2 was allowed in the case of stable disease and good tolerability of the drug. All 18 patients (median age 58 years) who enrolled were treated with gemcitabine, and all were assessable for toxicity, response and survival. Only two of these 18 patients had an objective response to a previous palliative chemotherapy. A median of 3 cycles (range 1-7) of gemcitabicin were administered. Two (11%) of the patients had a partial response lasting 5 and 6 months, respectively. Both of these patients had only lung metastases. Whereas one of these patients had a transient partial response to the foregoing chemotherapy (consisting of ifosfamide and doxorubicin), the other patient has been progressive on these drugs. One additional patient, progressive on ifosfamide and doxorubicin, had an objective response of greater than 50% confined to the lungs and stable local recurrence for 6 months. Six patients had stable disease for 3-6 months and nine patients had disease progression. The median survival was 8 months. Treatment generally was well tolerated with six patients having transient grade 3 non-hematologic toxicity, four having grade 3 neutropenia, and one having grade 4 neutropenia and thrombocytopenia. Gemcitabine, given as a prolonged infusion at a low dose level, has a favorable toxicity profile and displays antitumor activity in patients with intensively pretreated, advanced soft tissue sarcomas.
Insights
Low-dose gemcitabine infusions show antitumor activity in advanced soft tissue sarcomas. This treatment is well-tolerated in pretreated patients, offering a new option for this challenging cancer.
Area of Science:
- Oncology
- Medical Oncology
- Pharmacology
Background:
- Soft tissue sarcomas (STS) have limited treatment options due to the scarcity of effective cytotoxic drugs.
- There is a continuous need for novel anti-cancer agents with improved activity against STS.
Purpose of the Study:
- To evaluate the response rate of gemcitabine in patients with pretreated advanced soft tissue sarcomas.
- To define the toxicities associated with prolonged infusions of low-dose gemcitabine in this patient population.
Main Methods:
- A prospective Phase II clinical trial was conducted.
- Gemcitabine was administered as a 360-minute infusion on days 1, 8, and 15 of a 28-day cycle.
- Initial dose was 200 mg/m², with potential escalation to 250 mg/m².
Main Results:
- Two out of 18 patients (11%) achieved a partial response, both with lung metastases.
- One additional patient showed a significant partial response in lung metastases and stable local disease.
- Six patients had stable disease for 3-6 months; median survival was 8 months.
Conclusions:
- Low-dose, prolonged infusion gemcitabine demonstrates antitumor activity in heavily pretreated advanced soft tissue sarcomas.
- The treatment exhibits a favorable toxicity profile, with manageable non-hematologic and hematologic toxicities.
- This regimen represents a potential therapeutic option for patients with advanced STS who have limited treatment alternatives.