Lessons learned from a decade of clinical trials of high-dose chemotherapy in ovarian cancer

2008 ◽  
Vol 18 (Suppl 1) ◽  
pp. 53-58 ◽  
Author(s):  
J. A. Ledermann

Ovarian cancer is one of the most chemosensitive solid tumors and therefore a good example to explore high-dose chemotherapy (HDC). Interest in pursuing this treatment arose in the late 1980s following the success of HDC in treating hematological cancers and improvements in supportive care with peripheral blood stem cells. Experience from phase II trials and analysis of Bone Marrow Transplant Registry data led to the launch of several randomized phase III trials in the late 1990s. Initial enthusiasm for this treatment was in part due to the preliminary positive data emerging from HDC in breast cancer. Five randomized trials of HDC in ovarian cancer have been conducted and all experienced difficulty in recruitment. Their different designs and results are reviewed, as well as some of the lessons that have been learned about HDC in solid tumors in the last decade

2006 ◽  
Vol 42 (14) ◽  
pp. 2196-2199 ◽  
Author(s):  
Seija Grénman ◽  
Tom Wiklund ◽  
Jyrki Jalkanen ◽  
Tapio Kuoppala ◽  
Johanna Mäenpää ◽  
...  

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10505-10505
Author(s):  
N. N. Binh ◽  
C. Chevreau ◽  
N. Penel ◽  
J. Bay ◽  
J. Coindre ◽  
...  

10505 Background: Whether high dose (HD) chemotherapy improves disease-free (DFS) or overall (OS) survival has been suggested in phase II trial, but never explored in a randomized setting. This randomized, open, phase III study was designed to assess whether or not an HD chemotherapy with peripheral blood stem cells (PBSC) would improve OS in patients with advanced or metastatic STS responding to MAID chemotherapy. Methods: Pts aged 18 to 65 and with advanced STS were enrolled. After 4 courses of MAID, patients in PR or CR, or in whom complete surgical removal of all lesions was performed, were proposed for randomisation between 2 more cycles of MAID (control arm) vs 1 MAID followed by an intensification with MICE, ie: mesna (3.6g/m2, d1–5), ifosfamide (4g/m2, d1–4), carboplatin (UCA5, d2–4) and etoposide (300mg/m2, d1–4), followed by PBSC (HD arm). The primary endpoint was OS and the study was designed to detect by logrank test a 25% difference between the arms. Results: From 03/00 to 06/08, 266 patients were included and 87 were randomised (15 centres); low accrual and new treatment concepts lead to an IDMC in 11/08 who analysed 45 treated in the control arm (41 with full treatment) and 40 in the HD arm [only 21 received MICE, because consent withdrawal (6), insufficient PBSC harvest (5), tumor reprogression (4)]. Baseline characteristics (pts and tumors) were similar between treatment arms. With a 39 months follow-up, 25 pts were alive in the control arm, and 19 in the HD arm. The 3 years OS was 45.5% for control arm versus 35.8 for HD arm (HR = 1.12; 95% CI 0.58, 2.14; p = 0.72 Intention to treat analysis); PFS was 29.9% and 12.1 respectively (HR = 1.48; 95% CI 0.87, 2.53; p = 0.14). Higher rate of grade 3 - 4 hematologic (87% vs 46%), and digestive toxicity (33% vs 0%) were observed in the HD arm. Two treatment-related deaths occurred, both in the HD arm. Conclusions: In this study, HD chemotherapy for STS patients didn't improve OS and DFS. Consolidations with new concepts have to be explored. [Table: see text]


2006 ◽  
Vol 24 (1) ◽  
pp. 136-140 ◽  
Author(s):  
Andrew J. Vickers ◽  
Joyce Kuo ◽  
Barrie R. Cassileth

Purpose A substantial number of cancer patients turn to treatments other than those recommended by mainstream oncologists in an effort to sustain tumor remission or halt the spread of cancer. These unconventional approaches include botanicals, high-dose nutritional supplementation, off-label pharmaceuticals, and animal products. The objective of this study was to review systematically the methodologies applied in clinical trials of unconventional treatments specifically for cancer. Methods MEDLINE 1966 to 2005 was searched using approximately 200 different medical subject heading terms (eg, alternative medicine) and free text words (eg, laetrile). We sought prospective clinical trials of unconventional treatments in cancer patients, excluding studies with only symptom control or nonclinical (eg, immune) end points. Trial data were extracted by two reviewers using a standardized protocol. Results We identified 14,735 articles, of which 214, describing 198 different clinical trials, were included. Twenty trials were phase I, three were phase I and II, 70 were phase II, and 105 were phase III. Approximately half of the trials investigated fungal products, 20% investigated other botanicals, 10% investigated vitamins and supplements, and 10% investigated off-label pharmaceuticals. Only eight of the phase I trials were dose-finding trials, and a mere 20% of phase II trials reported a statistical design. Of the 27 different agents tested in phase III, only one agent had a prior dose-finding trial, and only for three agents was the definitive study initiated after the publication of phase II data. Conclusion Unconventional cancer treatments have not been subject to appropriate early-phase trial development. Future research on unconventional therapies should involve dose-finding and phase II studies to determine the suitability of definitive trials.


2006 ◽  
Vol 17 (10) ◽  
pp. 1479-1488 ◽  
Author(s):  
P. Pedrazzoli ◽  
J.A. Ledermann ◽  
J.-P. Lotz ◽  
S. Leyvraz ◽  
M. Aglietta ◽  
...  

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