Abstract
Background: The purpose of this study was to evaluate risk and response–based multi-agent therapy for patients with rhabdomyosarcoma (RMS) at first relapse. Methods: Patients with RMS and measurable disease at first relapse with unfavorable-risk (UR) features were randomized to a 6-week phase 2 window with 1 of 2 treatment schedules of irinotecan with vincristine (VI) (previously reported). Those with at least a partial response to VI continued to receive 44 weeks of multi-agent chemotherapy including the assigned VI regimen. UR patients who did not have measurable disease at study entry, did not have a radiographic response after the VI window, or declined VI window therapy received 31 weeks of multi-agent chemotherapy including tirapazamine (TPZ) at weeks 1, 4, 10, 19, and 28. Favorable-risk (FR) patients received 31 weeks of the same multi-agent chemotherapy without VI and TPZ. Results: One hundred thirty-six eligible patients were enrolled. For 61 patients not responding to VI, the 3-year failure-free survival (FFS) and overall survival (OS) rates were 17% (95% confidence interval [CI], 8%-29%) and 24% (13%-37%), respectively. For 30 UR patients not treated with VI, the 3-year FFS and OS rates were 21% (8%-37%) and 39% (20%-57%), respectively. FR patients had 3-year FFS and OS rates of 79% (47%-93%) and 84% (50%-96%), respectively. There were no unexpected toxicities. Conclusions: Patients with UR RMS at first relapse or disease progression have a poor prognosis when they are treated with this multi-agent therapy, whereas FR patients have a higher chance of being cured with second-line therapy.
| Original language | English |
|---|---|
| Pages (from-to) | 2602-2609 |
| Number of pages | 8 |
| Journal | Cancer |
| Volume | 125 |
| Issue number | 15 |
| DOIs | |
| State | Published - Aug 1 2019 |
Bibliographical note
Publisher Copyright:© 2019 American Cancer Society
Funding
Leo Mascarenhas reports grants to his institution from AstraZeneca Pharmaceuticals LP; grants, nonfinancial support, and other to his institution from Eli Lilly and Company; personal fees for service in a speakers’ bureau (from October 1, 2018 to February 22, 2019) from Bayer Pharma AG; and grants to his institution from Novartis Pharmaceuticals Corporation, Merck Sharpe and Dome Corporation, and E.R. Squibb and Sons LLC for work performed outside the current study. Philip P. Breitfeld is employed by and owns stock in Quintiles, owns stock in and is a board member for Champions Oncology, and has received personal fees from Grid Therapeutics for work performed outside the current study. David A. Rodeberg reports travel, accommodation, and expenses from Navidea. James R. Anderson has received grants from the National Cancer Institute’s Cancer Therapy Evaluation Program for work performed as part of the current study; he also reports being employed by and owning stock in Merck and acting as a consultant for Merck, Amgen, and SFS Pharma. Douglas S. Hawkins reports that he was reimbursed for travel, lodging, and food to attend medical advisory board meetings for Loxo Oncology, Bristol-Myers Squibb, Celgene, and Bayer and that his institution received funds to cover the cost of conducting a clinical trial from Loxo Oncology, Lilly, Eisai, Merck Sharpe and Dome Corporation, Novartis, GlaxoSmithKline, and Sanofi. The other authors made no disclosures. This study was supported by the National Cancer Institute (grants U10CA180886, U10CA180899, U10CA98543, and U10CA98413). Leo Mascarenhas reports grants to his institution from AstraZeneca Pharmaceuticals LP; grants, nonfinancial support, and other to his institution from Eli Lilly and Company; personal fees for service in a speakers? bureau (from October 1, 2018 to February 22, 2019) from Bayer Pharma AG; and grants to his institution from Novartis Pharmaceuticals Corporation, Merck Sharpe and Dome Corporation, and E.R. Squibb and Sons LLC for work performed outside the current study.
| Funders | Funder number |
|---|---|
| AstraZeneca Pharmaceuticals AB | |
| Bayer Pharma AG | |
| Merck Sharpe and Dome Corporation | |
| National Cancer Institute’s Surveillance, Epidemiology and End Results Program | |
| National High Technology Development Program of China (863 Program) | |
| National Childhood Cancer Registry – National Cancer Institute | U10CA180886, U10CA98413, U10CA98543, U10CA180899 |
| AMGen | |
| Eli Lilly and Company | |
| Novartis Pharmaceuticals Corporation | |
| Society for French Historical Studies |
Keywords
- recurrent
- refractory
- relapse
- rhabdomyosarcoma
- treatment
ASJC Scopus subject areas
- Oncology
- Cancer Research
