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 "title": "Carboplatin and vincristine regimen",
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 "excerpt": "The carboplatin and vincristine regimen (CV) is a two-drug combination chemotherapy used mainly as frontline treatment for progressive or symptomatic pediatric low-grade glioma, except BRAF V600E-mutated tumors.",
 "snippet": "The carboplatin and vincristine regimen (CV) is a two-drug combination chemotherapy used mainly as frontline treatment for progressive or symptomatic pediatric low-grade glioma, except BRAF V600E-mutated tumors.",
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 "markdown": "# Carboplatin and vincristine regimen\n\nThe carboplatin and vincristine regimen (CV) is a two-drug combination chemotherapy used mainly to treat progressive or symptomatic pediatric low-grade glioma. Cytotoxic chemotherapy of this type remains the standard frontline treatment for children whose tumors require therapy, with the exception of BRAF V600E-mutated tumors, where targeted agents are now preferred.<sup>[1](https://academic.oup.com/neuro-oncology/article/28/9/2110/8687684)</sup>\n\n| Key fact | Detail |\n|---|---|\n| Main indication | Frontline chemotherapy for progressive or symptomatic pediatric low-grade glioma, except BRAF V600E-mutated tumors<sup>[1](https://academic.oup.com/neuro-oncology/article/28/9/2110/8687684)</sup> |\n| WHO status | Carboplatin and vincristine listed on the EML/EMLc for low-grade glioma as standard of care<sup>[2](https://list.essentialmeds.org/recommendations/1247)</sup> |\n| Classic (Packer) schedule | Carboplatin 175 mg/m² by 1-hour infusion weekly (4 weeks on, 2 weeks rest, 4 weeks on); vincristine 1.5 mg/m² (maximum 2 mg) weekly for 10 weeks, then maintenance<sup>[3](https://doi.org/10.3171/jns.1997.86.5.0747)</sup> |\n| Efficacy (1997 series) | 56% objective response; progression-free survival 75 ± 6% at 2 years and 68 ± 7% at 3 years<sup>[3](https://doi.org/10.3171/jns.1997.86.5.0747)</sup> |\n| Randomized comparison (COG A9952) | 5-year event-free survival 39% ± 4% for CV versus 52% ± 5% for TPCV<sup>[4](https://doi.org/10.1200/jco.2011.36.6054)</sup> |\n| NF1 advantage | 5-year EFS 69% ± 4% in NF1 versus 39% ± 4% in non-NF1 children treated with CV<sup>[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC4892942/)</sup> |\n| Targeted-therapy comparison | Dabrafenib plus trametinib in BRAF V600E tumors: response 47% versus 11%, median PFS 20.1 versus 7.4 months<sup>[6](https://link.springer.com/article/10.1007/s12672-026-04639-4)</sup> |\n\n## How it works\n\nThe World Health Organization Expert Committee has extended the Essential Medicines List listings for carboplatin, cisplatin, cyclophosphamide, vinblastine, and vincristine to include low-grade glioma, recognizing these protocols as standard of care.<sup>[2](https://list.essentialmeds.org/recommendations/1247)</sup>\n\n## How it is done\n\nIn the classic schedule, carboplatin is given by a 1-hour infusion at 175 mg/m² for 4 consecutive weeks, followed by a 2-week rest and then 4 more weeks, while vincristine at 1.5 mg/m² (maximum dose 2 mg) is given by intravenous bolus weekly for 10 weeks; this induction is followed by 12 maintenance cycles.<sup>[3](https://doi.org/10.3171/jns.1997.86.5.0747)</sup> The Children's Oncology Group (COG) trial NCT00002944 used the same 10-week induction followed by 2 weeks of rest, then 8 maintenance cycles, each consisting of 4 weekly carboplatin doses and 3 weekly vincristine doses followed by 2 weeks of rest.<sup>[7](https://clinicaltrials.gov/study/NCT00002944)</sup>\n\nThe SIOP-LGG 2004 protocol uses a denser carboplatin schedule: induction is 10 weekly doses of vincristine 1.5 mg/m² by IV bolus plus four doses of carboplatin 550 mg/m² by IV infusion at 3-week intervals, followed by three cycles of simultaneous vincristine and carboplatin at 4-week intervals.<sup>[2](https://list.essentialmeds.org/recommendations/1247)</sup>\n\n## Origin\n\nThe weekly carboplatin dose used in the combination came from an earlier single-agent study. Allen and colleagues reported in 1987 in the Journal of Clinical Oncology that the phase I maximum tolerable dose of carboplatin in children with recurrent brain tumors was 210 mg/m²/week and recommended 175 mg/m²/week for subsequent pediatric phase II studies; 9 of 36 (25%) evaluable patients had objective responses, and the drug showed low auditory, renal, and emetic toxicity.<sup>[8](https://doi.org/10.1200/jco.1987.5.3.459)</sup> In 1989, a study was begun to evaluate combining carboplatin and vincristine in children with recurrent and newly diagnosed astrocytomas.<sup>[3](https://doi.org/10.3171/jns.1997.86.5.0747)</sup>\n\nThe preliminary report by Packer, Lange, Ater, and colleagues in 1993 treated 23 children with recurrent and 37 with newly diagnosed low-grade gliomas with the 10-week induction followed by maintenance, and concluded that the drugs have activity in both settings.<sup>[9](https://www.ovid.com/journals/jclon/pdf/10.1200/jco.1993.11.5.850~carboplatin-and-vincristine-for-recurrent-and-newly)</sup> The 1997 follow-up by Packer and colleagues in the Journal of Neurosurgery reported 78 children with newly diagnosed progressive disease.<sup>[3](https://doi.org/10.3171/jns.1997.86.5.0747)</sup> The regimen then became a standard comparator in cooperative-group trials: COG A9952 (NCT00002944), started in April 1997 with 428 patients enrolled, randomized CV against thioguanine, procarbazine, lomustine, and vincristine (TPCV).<sup>[7](https://clinicaltrials.gov/study/NCT00002944)</sup>\n\n## Variants\n\nThe main schedule variants are weekly versus 3-weekly carboplatin. The Packer and COG schedules use weekly 175 mg/m² dosing; SIOP-LGG 2004 uses 550 mg/m² at 3-week intervals.<sup>[2](https://list.essentialmeds.org/recommendations/1247)</sup> Single-agent carboplatin is also used alone: a Pediatric Oncology Group phase II study treated 50 children with progressive optic pathway tumors using carboplatin 560 mg/m² every 4 weeks for up to 18 months.<sup>[10](https://europepmc.org/articles/PMC1920597)</sup>\n\nAdding a third drug did not help. In SIOP-LGG 2004, adding etoposide to CV gave no survival advantage: 5-year progression-free survival was 46% versus 45% and overall survival 89% in both arms.<sup>[2](https://list.essentialmeds.org/recommendations/1247)</sup> When grade II or worse carboplatin hypersensitivity develops, the SIOP protocol recommends replacing carboplatin with cycles of cisplatin 30 mg/m² on days 1 and 2 plus cyclophosphamide 1500 mg/m² on day 1.<sup>[2](https://list.essentialmeds.org/recommendations/1247)</sup>\n\n## Applications\n\nThe 1997 series of 78 children (mean age 3 years, range 3 months to 16 years) showed 44 (56%) objective responses, with progression-free survival of 75 ± 6% at 2 years and 68 ± 7% at 3 years; children 5 years old or younger at the time of treatment had a 3-year progression-free survival rate of 74 ± 7% compared with 39 ± 21% in older children.<sup>[3](https://doi.org/10.3171/jns.1997.86.5.0747)</sup>\n\nIn COG A9952, 274 eligible children were randomized equally; 5-year event-free survival and overall survival for all eligible patients were 45% ± 3.2% and 86% ± 2.2%, and the 5-year event-free survival was 39% ± 4% for CV versus 52% ± 5% for TPCV (cure model analysis \\( P = .007 \\)).<sup>[4](https://doi.org/10.1200/jco.2011.36.6054)</sup> A later COG analysis of NF1 children treated with CV on A9952 found 5-year event-free survival of 69% ± 4% versus 39% ± 4% for non-NF1 children (\\( P < 0.001 \\)) and overall survival of 98% ± 1% versus 87% ± 3% (\\( P = 0.003 \\)).<sup>[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC4892942/)</sup> Event-free and progression-free survival figures for first-line CV differ between reports: 5-year event-free survival of 39% ± 4% in A9952<sup>[4](https://doi.org/10.1200/jco.2011.36.6054)</sup> versus 53% in a retrospective cohort, which also noted higher values for NF1-associated tumors.<sup>[11](https://pmc.ncbi.nlm.nih.gov/articles/PMC9555059/)</sup>\n\n## Limitations and alternatives\n\nOn COG A9952, cumulative grade 3–4 toxicity included peripheral nervous system toxicity in 19% (CV) and 23% (CV-NF1), allergy in 10% and 8%, and infection in 23% and 18%.<sup>[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC4892942/)</sup> In a dedicated neurotoxicity study of 21 pediatric patients, peripheral neuropathy was present in 86%, and 8 patients (38%) required vincristine dose reduction for grade III toxicity; most neurotoxicity occurred during induction or the first maintenance cycle, and no ototoxicity was observed.<sup>[12](https://doi.org/10.1002/pbc.27351)</sup> Three second malignant neoplasms occurred among NF1 patients receiving CV at a median of 7.8 years (range 7.3 to 9.4 years) after enrollment, and none in the non-NF1 group.<sup>[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC4892942/)</sup>\n\nOne cohort documented carboplatin hypersensitivity in 47% of patients, with a strong protocol dependence: 8% with 4-weekly single-agent carboplatin versus 68% with 3-weekly combined CV per the SIOP 2004 protocol (OR 23.6, \\( P < 0.01 \\)).<sup>[13](https://onlinelibrary.wiley.com/doi/10.1002/pbc.25686)</sup> Across studies, reported frequency ranges from 7% to 78%, with the first reaction after a median of 7 to 9 doses.<sup>[14](https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00179/full)</sup> Rechallenge after hypersensitivity is contested: in one cohort, desensitization succeeded in only 2 of 10 patients in whom it was attempted,<sup>[13](https://onlinelibrary.wiley.com/doi/10.1002/pbc.25686)</sup> while a desensitization protocol succeeded in 100% of one cohort, against literature success rates of 20–75%.<sup>[14](https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00179/full)</sup> Substitution options include the cisplatin and cyclophosphamide replacement noted above<sup>[2](https://list.essentialmeds.org/recommendations/1247)</sup> or switching drugs entirely.\n\nThe nearest chemotherapy alternative is weekly vinblastine. A phase II study of weekly vinblastine in recurrent or refractory pediatric low-grade glioma was reported by Bouffet and colleagues in 2012 in the Journal of Clinical Oncology.<sup>[15](https://doi.org/10.1200/jco.2011.34.5843)</sup>\n\nIn a randomized phase 2 trial of dabrafenib plus trametinib versus CV as first-line therapy in BRAF V600E-mutant patients, the targeted combination achieved an objective response rate of 47% versus 11%, median progression-free survival of 20.1 versus 7.4 months, and grade 3/4 adverse events in 47% versus 94%.<sup>[6](https://link.springer.com/article/10.1007/s12672-026-04639-4)</sup> This led to the first FDA approval of upfront targeted therapy for pediatric low-grade glioma, and the FDA and [European Medicines Agency](https://www.edgepedia.org/european-medicines-agency) approved dabrafenib plus trametinib in 2023 for patients 1 year or older with BRAF V600E-altered low-grade glioma.<sup>[16](https://academic.oup.com/neuro-onc-peds/article/2/2/wuag019/8644343)</sup><sup> • </sup><sup>[1](https://academic.oup.com/neuro-oncology/article/28/9/2110/8687684)</sup> For tumors without BRAF V600E mutations, two phase 3 trials are testing selumetinib against standard CV as frontline therapy: NCT03871257 in NF1-associated disease and NCT04166409 in non-NF1 disease.<sup>[6](https://link.springer.com/article/10.1007/s12672-026-04639-4)</sup> Direct comparison of 2-year progression-free survival between CV (about 60%) and selumetinib (about 70%) is confounded by different therapy durations; at 5 years, selumetinib rates of 30.8% (non-NF1) and 54.2% (NF1) appear more equivocal with CV's 39% (non-NF1) and 69% (NF1).<sup>[1](https://academic.oup.com/neuro-oncology/article/28/9/2110/8687684)</sup> CV therefore retains its place as the standard frontline chemotherapy for children without BRAF V600E-mutated tumors while those trials mature.\n\n## References\n\n1. [Tempered optimism: Advances in the precision medicine era for pediatric low-grade glioma (Neuro-Oncology)](https://academic.oup.com/neuro-oncology/article/28/9/2110/8687684)\n2. [eEML - Electronic Essential Medicines List: carboplatin, cisplatin, cyclophosphamide, vinblastine and vincristine for low-grade glioma](https://list.essentialmeds.org/recommendations/1247)\n3. [Roger J. Packer and colleagues (1997). Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas. Journal of neurosurgery.](https://doi.org/10.3171/jns.1997.86.5.0747)\n4. [Joann L. Ater and colleagues (2012). Randomized Study of Two Chemotherapy Regimens for Treatment of Low-Grade Glioma in Young Children: A Report From the Children's Oncology Group. Journal of Clinical Oncology.](https://doi.org/10.1200/jco.2011.36.6054)\n5. [Non-randomized Comparison between NF1 and Non-NF1 Children Who Received Carboplatin and Vincristine (CV) for Progressive Low Grade Glioma: a Report from the Children's Oncology Group](https://pmc.ncbi.nlm.nih.gov/articles/PMC4892942/)\n6. [Molecular convergence enables precision medicine for pediatric low grade gliomas (Discover Oncology)](https://link.springer.com/article/10.1007/s12672-026-04639-4)\n7. [Combination Chemotherapy in Treating Children With Progressive Brain Tumors (NCT00002944, COG A9952 phase III CV vs TPCV)](https://clinicaltrials.gov/study/NCT00002944)\n8. [J C Allen and colleagues (1987). Carboplatin and recurrent childhood brain tumors.. Journal of Clinical Oncology.](https://doi.org/10.1200/jco.1987.5.3.459)\n9. [Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood (Packer et al., J Clin Oncol 11(5):850-856, 1993)](https://www.ovid.com/journals/jclon/pdf/10.1200/jco.1993.11.5.850~carboplatin-and-vincristine-for-recurrent-and-newly)\n10. [Carboplatin is effective therapy for young children with progressive optic pathway tumors: a Pediatric Oncology Group phase II study (Mahoney et al., Neuro-Oncology 2000)](https://europepmc.org/articles/PMC1920597)\n11. [Efficacy of different salvage regimens in progressive unresectable pediatric low-grade glioma](https://pmc.ncbi.nlm.nih.gov/articles/PMC9555059/)\n12. [Carboplatin and vincristine neurotoxicity in the treatment of pediatric low-grade gliomas (Pediatric Blood & Cancer, via aggregator copy)](https://doi.org/10.1002/pbc.27351)\n13. [Carboplatin Hypersensitivity Reactions in Pediatric Low Grade Glioma Are Protocol Specific and Desensitization Shows Poor Efficacy (Pediatric Blood & Cancer)](https://onlinelibrary.wiley.com/doi/10.1002/pbc.25686)\n14. [Rechallenge to Carboplatin in Children with Low Grade Glioma and Carboplatin Hypersensitivity Reactions (Frontiers in Pharmacology)](https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00179/full)\n15. [Eric Bouffet and colleagues (2012). Phase II Study of Weekly Vinblastine in Recurrent or Refractory Pediatric Low-Grade Glioma. Journal of Clinical Oncology.](https://doi.org/10.1200/jco.2011.34.5843)\n16. [Nationwide evaluation of MAPK inhibitors trametinib and dabrafenib for pediatric low-grade glioma in the United Kingdom (Neuro-Oncology Pediatrics)](https://academic.oup.com/neuro-onc-peds/article/2/2/wuag019/8644343)\n\n---\n*Topic: Encyclopedia › Life and health › Human health and medicine › Medicines and therapeutics › Cancer chemotherapy and regimens › Platinum-based regimens*\n\n*Initially written Sep 29, 2026 · Reviewed: Sep 30, 2026 · Edited: Sep 30, 2026 · Last review: Sep 30, 2026*\n\n*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*\n\nLicense: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license\n",
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 "speakable": "The carboplatin and vincristine regimen is a two-drug combination chemotherapy used mainly as frontline treatment for progressive or symptomatic pediatric low-grade glioma, except BRAF V600E-mutated tumors."
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