Related Experiment Video
Updated: Aug 8, 2026
Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma
Published on: April 11, 2018
Phase II study with the combination of gemcitabine and DTIC in patients with advanced soft tissue sarcomas
1Servicio de Oncología, Hospital Central de Asturias, 33006, Oviedo, Spain.
Purpose:
Based on the promising results of a Phase I study with a combination of gemcitabine and DTIC performed in advanced soft tissue sarcoma (ASTS) patients, and due to the limited efficacy of second or third line therapies in those patients, we designed a Phase II study to determine the activity of this new regimen.
Methods:
Patients with ASTS, measurable disease, pretreated with chemotherapy, received gemcitabine 1,800 mg/m2 infused over 180 min followed by DTIC 500 mg/m2 (one cycle), every 2 weeks. The pharmacokinetics (PK) of gemcitabine and 2',2'-difluorodeoxyuridine (dFdU), and the accumulation of gemcitabine triphosphate (dFdCTP) by peripheral blood mononuclear cells were studied. The influence of the sequence of administration on those parameters was examined to exclude potential drug interactions.
Results:
Twenty-six patients received a total of 158 cycles (mean four cycles, range 1-18). Grade 3-4 anemia (23% of patients), granulocytopenia (46%) or thrombocytopenia (12%), and grade 3 increase in AST (18%), ALT (21%), or gamma-glutamyl-transferase (9%) were noted. Response rate in 23 patients was 4% (95% CI: 0-24%), and in 8 of 11 patients stable disease lasted > 6 months. Progression-free rate (PFR) at 3 and 6 months was, respectively, 48 and 28%, and median overall survival 37 weeks. Pooled data from the Phase I and Phase II studies showed clinical benefit in patients with leiomyosarcomas (LMS) (57%) and malignant fibrous histiocytomas (MFH) (33%). The sequence of administration did not influence PK of gemcitabine or dFdU. There was a trend (P = 0.11) toward a lower accumulation of dFdCTP when DTIC preceded gemcitabine.
Conclusions:
Although the remission rate was low, PFR figures indicate that this regimen has activity in patients with ASTS. It should be compared with DTIC, or other gemcitabine-containing combinations, in patients with LMS or MFH, to determine whether this combination offers advantages in PFR or in overall activity.
Insights
This Phase II study evaluated gemcitabine plus DTIC for advanced soft tissue sarcoma (ASTS). While the remission rate was low, progression-free rates suggest activity, particularly in leiomyosarcomas and malignant fibrous histiocytomas.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Limited efficacy of second/third-line therapies in advanced soft tissue sarcoma (ASTS).
- Promising Phase I results with gemcitabine and DTIC combination therapy.
- Need for novel treatment strategies in advanced soft tissue sarcoma.
Purpose of the Study:
- To determine the anti-cancer activity of a gemcitabine and DTIC combination regimen in ASTS patients.
- To evaluate the pharmacokinetics (PK) of gemcitabine and DTIC, including drug accumulation.
- To assess the influence of drug administration sequence on PK parameters.
Main Methods:
- Phase II clinical trial enrolling pretreated ASTS patients with measurable disease.
- Gemcitabine (1,800 mg/m2) followed by DTIC (500 mg/m2) administered every two weeks.
- Pharmacokinetic analysis of gemcitabine, dFdU, and dFdCTP accumulation; sequence effects examined.
Main Results:
- Twenty-six patients received 158 cycles; common toxicities included anemia and granulocytopenia.
- Overall response rate was 4%; however, 8/11 patients achieved stable disease > 6 months.
- Progression-free rates at 3 and 6 months were 48% and 28%, respectively; median survival 37 weeks.
- Clinical benefit observed in leiomyosarcomas (57%) and malignant fibrous histiocytomas (33%).
- Drug sequence did not impact gemcitabine/dFdU PK; trend towards lower dFdCTP accumulation when DTIC preceded gemcitabine.
Conclusions:
- The gemcitabine and DTIC regimen shows activity in ASTS, indicated by progression-free rates.
- Further comparison with DTIC monotherapy or other gemcitabine combinations is warranted for LMS and MFH.
- The combination may offer advantages in progression-free rates or overall activity for specific subtypes.
