Article

Rationale and delineation of a composite index of relative antitumoural efficacy (In-RATE).

Hôpital Edouard-Herriot, Oncologie médicale, Pavillon E, 5 place d'Arsonval, 69437 Lyon Cedex 03, France.
Critical Reviews in Oncology/Hematology (Impact Factor: 4.05). 12/2007; 64(2):106-14. DOI: 10.1016/j.critrevonc.2007.04.013
Source: PubMed

ABSTRACT Over the last decades, the development of new drugs has allowed cancer patients to experience several lines of chemotherapy, the objective of which is a long term stabilization of the tumour. The objectives of this work was to delineate a composite index of relative antitumoural efficacy (In-RATE) of a regimen over another, including response rate (RR), median time to progression (TTP) and progression rate (PR). When considering two treatments a and b, the In-RATE was defined as RRa/RRb x TTPa/TTPb x PRb/PRa. Values significantly superior or inferior to 1 reveal an advantage for treatment a or b, respectively. The applicability of the In-RATE to published randomized trials in four frequent tumour types (colorectal, non-small cell lung, advanced ovarian and metastatic breast cancers) was suggested to more precisely distinguish the effects of different drugs, and sometimes to detect a significant difference when the published data did not conclude to statistical difference.

0 Followers
 · 
66 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this phase II study was to assess the benefits of a weekly administration of topotecan and gemcitabine in patients with ovarian carcinoma having relapsed after platinum/taxane-based first-line chemotherapy. Seventy-seven patients with progression of disease </=12 months after first-line chemotherapy were enrolled to receive topotecan (2.5 mg/m(2)) and gemcitabine (1000 mg/m(2)) on days 1, 8 and 15 (q 28 d). Primary endpoint was the response rate. Stabilization rate and symptom improvement were also assessed. All patients received the combination and 66 were evaluable (>/=2 cycles administered). The only major severe toxicity was neutropenia grades 3 (17%) and 4 (6%). Approximately 60% of the patients received the complete schedule of treatment, dose interruptions/delays being mainly due to moderate thrombocytopenia or neutropenia. The objective response rate was 14%, the values for patients having relapsed within 6 (n=30) and 6-12 (n=36) months being 7% and 20%, respectively. Median durations of response were 4.9 and 6.4 months and clinical benefit rates including stabilizations reached 63% and 69% in patients having relapsed within 6 or 6-12 months, respectively. Corresponding median overall survival was 7.5 and 15.6 months. Symptoms and pain were reduced in 64% and 39% of the patients concerned, respectively. In early relapse ovarian cancer, weekly combination of gemcitabine and topotecan has a modest objective response rate. However, a high proportion of patients experienced stable disease and symptom control leading to acceptable quality of life.
    Gynecologic Oncology 09/2009; 115(3):382-8. DOI:10.1016/j.ygyno.2009.08.024 · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Although the efficiency of oxaliplatin in patients with advanced ovarian cancer has been demonstrated, it is not commonly used. In cells, oxaliplatin is metabolized by the enzymes belonging to the glutathione-S-transferase (GST) family. Case: A 55-year-old woman with advanced ovarian cancer received 6 cycles of paclitaxel and carboplatin after debulking surgery. Six months later, she experienced a clinical recurrence. A second-line chemotherapy combining 500 mg/m(2) cyclophosphamide with 100 mg/m(2) oxaliplatin was initiated and maintained for 10 cycles. The patient thus experienced a second complete remission that lasted for 6 years. We found that she had deficient GSTM1 enzyme activity with homozygous deletion and normal GSTP1 and GSTT1 activities. Conclusion: The association of a homozygous deletion of GSTM1 with hypersensitivity to oxaliplatin and cyclophosphamide combination chemotherapy has not been described to date in ovarian cancer. Further study of its potential interest to personalized second-line therapy in these patients is called for. © 2014 S. Karger AG, Basel.
    Chemotherapy 01/2014; 59(4):290-293. DOI:10.1159/000357517 · 1.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Over the last decade, the development of new therapeutic options has made more patients benefit from antitumoral strategies including several lines of chemotherapy, the aim of which is a long-term control of the disease progression. In such a context of "chronic" management, the choice of tumor response as a single parameter appears restrictive to assess those new therapeutic options. For that reason, we have recently proposed a composite index of relative efficacy including response rate as well as parameters related to tumour stabilization and duration of the response. The objective of this index, published as the In-RATE is to allow the comparison of two treatments a and b as follows: In-RATE a/b = (response rate a/response rate b) x (time to progression a/time to progression b) x (progression rate b/progression rate a). Values significantly higher or less than 1 suggest the superiority, in terms of efficacy, of treatments a or b, respectively. When retrospectively applied to randomised studies, the In-RATE showed that some results and conclusions based on the response rate as a unique endpoint might be reconsidered, and that a significant difference between protocols could be detected in published reports having concluded to statistical equivalence. This paper reviews the rationale and principle of this work, and discusses the potential clinical applications of the In-RATE.
    Bulletin du cancer 12/2008; 95(11):1075-82. DOI:10.1684/bdc.2008.0738 · 0.64 Impact Factor