Maintenance Chemotherapy for Patients with Rhabdomyosarcoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. The Rationale for Maintenance in RMS
3. The EpSSG Studies
4. Other Experience of MC in RMS
5. Discussion
6. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Author, Year of Publication (Reference) | Study | Patients | Type of Study (No of Pts) | Maintenance Chemotherapy | Conclusion |
---|---|---|---|---|---|
Bisogno et al., 2019 [8] | RMS2005—international multicentre | High-risk localized RMS | Randomized (371 pts enrolled, 185 received MC) | 6 cycles of i.v. vinorelbine 25 mg/m2 on days 1, 8, 15 and oral cyclophosphamide 25 mg/m2/day, on days 1 to 28. | Maintenance chemotherapy significantly increases patient OS (DFS increase was evident but not statistically significant) |
Gallego et al., 2018 [19] | RMS2005—international multicentre | Very high risk localized RMS | Prospective (103 pts) | Same as RMS2005 study | The contribution of MC to OS and EFS difficult to establish. Prognostic impact of fusion status |
Schoot et al., 2022 [20] | MTS2008—international multicentre | Metastatic RMS | Prospective (270 pts) | Same as RMS2005 study but longer (12 cycles) | The outcome remains poor. Not possible to determine whether the addition of MC improved the outcome in comparison with historical cohorts. |
Chisholm et al., 2017 [21] | BERNIE—international multicentre | Metastatic soft tissue sarcomas | Randomized phase II | Same as in MTS2008 study with the addition of Bevacizumab in the experimental arm | The outcome was not improved by the addition of Bevacizumab |
Klingebiel et al., 2008 [22] | HD CWS-96—international multicentre | Metastatic RMS | Prospective non randomized (96 pts enrolled, 51 received MC) | 4 cycles of trofosfamide (2 × 75 mg/m2/day) and idarubicine (1x5 mg/m2/day 1, 4, 7, 10) alternating with 4 cyles of trofosfamide and etoposide (2 × 25 mg/m2/day) | Significantly superior survival for patients receiving oral MC vs. those receiving high-dose chemotherapy |
Dantonello et al., 2010 [23] | CWS-91, CWS-86, CWS-91, CWS-96—international multicentre | Embryonal RMS with isolated lung metastasis | Retrospective (29 pts, 8 received MC) | Same as HD CWS-96 study | 5-years EFS was significantly superior in patients receiving MC |
Koscielniak et al., 2022 [24] | CWS2002P—international multicentre | High-risk localized soft tissue sarcomas | Prospective non randomized (204 pts enrolled, 155 pts received MC) | 7 cycles of i.v. vinblastine 3 mg/m2 on days 1, 8, and 15 and oral cyclophosphamide 2× 25 mg/m2/day on days 1–21. One week pause between the cycles | EFS and OS were significantly superior for patients receiving MC |
Koscielniak et al., 2022 [25] | CWS-2007 HR—international multicentre | High-risk localized soft tissue sarcomas | Randomized 195 enrolled, 96 received MC) | As in the HD CWS-96 study | OS and EFS were not different in the 2 groups |
Tramsen et al., 2023 [26] | CWS IV-2002 and CWS DOK IV 2004—international multicentre | Metastatic RMS | Prospective non randomized (176 pts enrolled, 89 received MC) | Same as in the HD CWS-96 study (14 pts) or as in the CWS2002P study (75 pts) | MC produces better results than allogenic bone marrow transplant and similar results when compared to high-dose chemotherapy but with a less therapeutic burden |
Devadas et al., 2019 [27] | Institutional study | Relapsed/refractory or metastatic sarcomas | Retrospective (13 RMS pts) | Oral tamoxifen 40 mg/m2/day divided twice every day, associated with etoposide and cyclophosphamide, both drugs were given orally at the dose of 50 mg/m2 for 21 days every 28 days, for at least 1 year. | MC is a low-cost treatment that can induce long-term remission in few patients |
El Kababri M et al., 2020 [28] | Multicentre study | Refractory or relapsing solid tumors | Prospective (14 RMS pts) | cyclophosphamide (30 mg/m2) and etoposide (25 mg/m2) days 1–21, followed by a break of one week and daily valproic acid (20 mg/kg) days 1–28. All drugs were given orally | The regimen demonstrated activity against sarcoma (3 responses in RMS pts) |
Lan Y et al., 2023 [29] | Institutional study | Newly diagnosed high-risk and relapsed RMS | Retrospective (57 pts) | Sam as RMS2005 study (but vinorelbine was administered orally and at a lower dose) Duration 48 weeks | Interesting results in relapsed non-metastatic pts (3-year OS 70%) |
RMS2005 | CWS2007 | |
---|---|---|
Standard chemotherapy before maintenance chemotherapy | 9 cycles of Ifosfamide, vincristine, actinomycin-D +/− doxorubicin | 9 cycles of Ifosfamide, vincristine, actinomycin-D +/− doxorubicin |
Eligible patients | High-risk localized RMS * | High-risk localized RMS * Undifferentiated sarcoma Extraskeletal Ewing sarcoma Nonresectable Synovial sarcoma |
Maintenance chemotherapy | 6 cycles of intravenous vinorelbine 25 mg/m2 on days 1, 8, 15 and daily oral cyclophosphamide 25 mg/m2, days 1–28 | Eight 10-day courses consisting of trofosfamide (2 × 75 mg/m2/day) and idarubicine (×5 mg/m2/day 1, 4, 7, 10) alternating with trofosfamide and etoposide(2 × 25 mg/m2/day). All drugs were given orally |
Patients randomized | 371 (186 vs. 185) | 195 (99 vs. 96) |
Median Follow-up | 60.3 months (IQR 32·4–89·4) | 4.9 years (IQR 3.0–5.7) |
Results ** | ||
DFS/EFS standard arm vs. maintenance chemotherapy arm | 69.8% vs. 77.6% (p = 0.06) | 75% vs. 66.2% (p = 0.07) |
OS standard arm vs. maintenance chemotherapy arm | 73.7% vs. 86.5% (p = 0.009) | 84.6% vs. 81.9% (p = 0.15) |
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Bisogno, G.; Minard-Colin, V.; Jenney, M.; Ferrari, A.; Chisholm, J.; Di Carlo, D.; Hjalgrim, L.L.; Orbach, D.; Merks, J.H.M.; Casanova, M. Maintenance Chemotherapy for Patients with Rhabdomyosarcoma. Cancers 2023, 15, 4012. https://doi.org/10.3390/cancers15154012
Bisogno G, Minard-Colin V, Jenney M, Ferrari A, Chisholm J, Di Carlo D, Hjalgrim LL, Orbach D, Merks JHM, Casanova M. Maintenance Chemotherapy for Patients with Rhabdomyosarcoma. Cancers. 2023; 15(15):4012. https://doi.org/10.3390/cancers15154012
Chicago/Turabian StyleBisogno, Gianni, Veronique Minard-Colin, Meriel. Jenney, Andrea Ferrari, Julia Chisholm, Daniela Di Carlo, Lisa Lyngsie Hjalgrim, Daniel Orbach, Johannes Hendrikus Maria Merks, and Michela Casanova. 2023. "Maintenance Chemotherapy for Patients with Rhabdomyosarcoma" Cancers 15, no. 15: 4012. https://doi.org/10.3390/cancers15154012