What is the PCV (procarbazine, lomustine, and vincristine) regimen for an adult patient with glioma, specifically anaplastic oligodendroglioma or anaplastic astrocytoma?

PCV Regimen in Glioma

Standard Dosing Protocol

For adult patients with anaplastic oligodendroglioma or anaplastic astrocytoma, the PCV regimen consists of procarbazine 60 mg/m² orally daily on days 8-21, lomustine 110 mg/m² orally once on day 1, and vincristine 1.4 mg/m² IV on days 8 and 29, administered in 8-week cycles for a total of six cycles. 1

Molecular Subtype-Specific Recommendations

IDH-Mutant, 1p19q-Codeleted Anaplastic Oligodendroglioma (Grade 3)

• Radiation therapy: 59.4 Gy in 33 fractions at five fractions per week 1
• Followed by adjuvant PCV using the standard dosing above 1
• This is a Category 1 recommendation based on significant overall survival benefit (HR 0.56 for OS in 1p19q-codeleted tumors) 1, 2
• Median OS reaches 112 months or longer with RT/PCV versus 42.3 months with RT alone 2
• The 1p19q codeletion confers both better prognosis and superior response to PCV (OS HR 0.21, P=0.029) 1

IDH-Mutant, 1p19q Non-Codeleted Anaplastic Astrocytoma (Grade 3)

• Radiation therapy: 59.4 Gy in 33 fractions of 1.8 Gy 1
• Adjuvant temozolomide is preferred over PCV (150-200 mg/m² days 1-5 every 4 weeks for maximum 12 months) 1
• PCV remains a Category 2A alternative with lesser benefit compared to oligodendroglioma (OS HR 0.38, P=0.013 for non-codeleted tumors) 1
• IDH-mutant tumors without 1p19q codeletion derive some benefit from PCV (OS HR 0.59) but less than codeleted tumors 1

IDH-Wildtype Tumors

• PCV provides no survival benefit in IDH-wildtype gliomas (OS HR 0.96, P=0.94) 1
• Standard glioblastoma treatment with temozolomide-based chemoradiation is preferred 1

Grade 2 Oligodendroglioma (IDH-Mutant, 1p19q-Codeleted)

• Radiation: 54 Gy in 30 fractions over 6 weeks 1
• Followed by adjuvant PCV using standard dosing 1
• Based on RTOG 9802 trial demonstrating survival benefit in lower-grade tumors 1

Timing Considerations: Neoadjuvant vs Adjuvant

Neoadjuvant PCV (Before Radiation)

• Used in RTOG 9402 trial: 4 cycles of PCV followed by RT 1
• Significant OS benefit in 1p19q-codeleted tumors (HR 0.67, P=0.01) 1
• Higher discontinuation rate (52% failed to complete treatment) 1

Adjuvant PCV (After Radiation)

• Used in EORTC 26951 trial: RT followed by 6 cycles of PCV 1, 3, 2
• Improved both PFS (24.3 vs 13.2 months) and OS (42.3 vs 30.6 months) 2
• Adjuvant approach is more commonly recommended due to better completion rates 1

Critical Toxicity Management

Expected Hematologic Toxicity

• Grade 3/4 hematologic adverse events occur in 56% of patients during PCV 1
• Most common: myelosuppression with thrombocytopenia (70.4% in standard PCV) 4
• 20% discontinue due to toxicity 1
• 38% of patients in EORTC 26951 discontinued adjuvant PCV for toxicity 3

Dose Modifications

• Modified PC regimen (omitting vincristine, reducing lomustine) shows significantly lower toxicity 4
• Thrombocytopenia reduced from 70.4% to 20.0% (P<0.001) 4
• Anemia reduced from 45.5% to 6.7% (P=0.02) 4
• Clinical impacts (cycle delays, dose reductions) reduced from 68.2% to 26.7% (P=0.012) 4
• Consider modified PC regimen in recurrent disease or patients with poor tolerance 4

Monitoring Requirements

• Check complete blood counts before each cycle 1
• Delay treatment if absolute neutrophil count <1,500/μL or platelets <100,000/μL 1
• Monitor liver function tests due to procarbazine hepatotoxicity 1

Common Pitfalls to Avoid

Drug Interactions

• Avoid enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital) as they interfere with PCV metabolism 1
• Use levetiracetam or lamotrigine for seizure control instead 1
• Temozolomide does not interact with enzyme-inducing anticonvulsants, but PCV does 1

Treatment Selection Errors

• Do not use PCV in IDH-wildtype tumors - no survival benefit demonstrated 1
• Do not delay molecular testing - 1p19q and IDH status are essential for treatment selection 1, 2
• In 1p19q non-codeleted anaplastic astrocytoma, temozolomide is preferred over PCV based on CATNON trial data 1

Completion Challenges

• 52% of patients fail to complete neoadjuvant PCV versus 10% for RT alone 1
• Plan for 6 cycles but anticipate dose modifications or early discontinuation 3
• 82% of patients in RT-only arm received chemotherapy at progression, suggesting delayed treatment is viable 3

Alternative Regimens

Temozolomide as Alternative

• No difference in efficacy between PCV and temozolomide in oligodendroglioma 1
• Temozolomide has better tolerability profile 1
• For 1p19q non-codeleted tumors, temozolomide is preferred 1

Recurrent Disease After Prior PCV

• Temozolomide shows 25% response rate as second-line therapy after PCV failure 5
• Median time to progression for responders: 8.0 months 5
• Consider modified PC regimen (without vincristine) for better tolerability 4

Evidence Quality Assessment

The PCV recommendations are based on:

• Level I evidence from two landmark randomized trials: EORTC 26951 and RTOG 9402 1, 3, 2
• Long-term follow-up (140 months median) confirming sustained OS benefit 2
• Consistent molecular subgroup analyses showing 1p19q codeletion predicts PCV benefit 1, 2
• 2022 ASCO-SNO guidelines provide the most current synthesis 1