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1.
Ann Oncol ; 24(2): 537-542, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23117071

ABSTRACT

BACKGROUND: The growth modulation index (GMI) is the ratio of time to progression with the nth line (TTP(n)) of therapy to the TTP(n)(-1) with the n-1th line. GMI >1.33 is considered as a sign of activity in phase II trials. PATIENTS AND METHODS: This retrospective analysis evaluated the concordance between the GMI and the efficacy outcomes in 279 patients with advanced soft tissue sarcoma (ASTS) treated with trabectedin 1.5 mg/m² (24-h infusion every 3 weeks) in four phase II trials. RESULTS: One hundred and forty-two (51%) patients received one prior line and 137 ≥ 2 lines. The median TTP(n) was 2.8 months (range 0.2-26.8), whereas the median TTP(n)(-1) was 4.0 months (0.3-79.5). The median GMI was 0.6 (0.0-14.4). Overall, 177 patients (63%) had a GMI <1; 21 (8%) a GMI equal to 1-1.33 and 81 (29%) a GMI >1.33, which correlated with the median overall survival in those patients (9.1, 13.9 and 23.8 months, respectively, P = 0.0005). A high concordance rate between the GMI and response rate (P < 0.0001) and progression-free survival (PFS, P < 0.0001) was observed. Good performance status (PS) was the only factor associated with GMI >1.33 (PS = 0; P < 0.04). CONCLUSIONS: A high GMI was associated with favorable efficacy outcomes in patients treated with trabectedin. Further research is needed to assess GMI as an indicator in this setting.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Cell Proliferation/drug effects , Dioxoles/therapeutic use , Sarcoma/drug therapy , Tetrahydroisoquinolines/therapeutic use , Adult , Aged , Aged, 80 and over , Antibiotics, Antineoplastic/therapeutic use , Disease-Free Survival , Doxorubicin/therapeutic use , Female , Humans , Male , Middle Aged , Retrospective Studies , Salvage Therapy , Sarcoma/metabolism , Sarcoma/mortality , Sarcoma/pathology , Trabectedin , Treatment Outcome , Young Adult
2.
Eur J Cancer ; 45(12): 2116-22, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19419856

ABSTRACT

AIM OF THE STUDY: To define the maximum tolerated dose (MTD) and toxicity of trabectedin (T) and cisplatin (C) given on days 1 and 8 every 3 weeks to adult patients with advanced solid tumours. Plasma pharmacokinetics at cycle 1 and a preliminary anti-tumour activity assessment in ovarian and non-small cell lung cancer (OC, NSCLC) were secondary objectives. METHODS: In the dose finding part (DFP) of the study the dose of T given at each administration was escalated by 100 microg/m(2) increments from 300 microg/m(2) up to the MTD, with a fixed dose of C of 40 mg/m(2). The recommended dose (RD) was assessed in the previously treated and untreated OC and NSCLC patients in the expansion of the RD (ERD) part of the study. T was administered with corticosteroids pre-medication as 3-h infusion and C as 30-min infusion. RESULTS: Thirty-nine patients were treated in the DFP and 10 in the ERD. The MTD of T was 700 microg/m(2) due to dose-limiting neutropaenia and the RDs in the previously treated/untreated patients were 500 and 600 microg/m(2), respectively. Most common toxicities were nausea/vomiting (67%), asthenia/fatigue (55%) and reversible ASAT/ALAT elevation (51%). Time to recovery from myelosuppression was dose-dependent and treatment could be repeated after > or = 4 weeks in the majority of patients at 600 microg/m(2). Confirmed partial responses were observed in 4 of 13 evaluable OC patients and in 1 with uterine leiomyosarcoma. No pharmacokinetic interaction was observed. CONCLUSION: The administration of T and C on days 1 and 8 resulted in prolonged neutropaenia requiring treatment delay. The evaluation of a single every 3 week schedule is worthwhile because of the hints of anti-tumour activity observed in OC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/adverse effects , Dioxoles/adverse effects , Lung Neoplasms/drug therapy , Ovarian Neoplasms/drug therapy , Tetrahydroisoquinolines/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cisplatin/administration & dosage , Cisplatin/pharmacokinetics , Dioxoles/administration & dosage , Dioxoles/pharmacokinetics , Female , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Maximum Tolerated Dose , Neutropenia/chemically induced , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Tetrahydroisoquinolines/administration & dosage , Tetrahydroisoquinolines/pharmacokinetics , Trabectedin
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