Compliance, adverse events and quality of life of patients in a phase 3 study comparing temozolomide with PCV as adjuvant chemotherapy in grade 2 and 3 glioma.
Authors: Menon Nandini Sharrel , Gupta Tejpal , Chatterjee Abhishek , Choudhary Amit , Puranik Ameya , Sridhar Epari , Dasgupta Archya , Sahay Ayushi , Moiyadi Aliasgar , Shetty Prakash , Singh Vikas Kumar , Pathak Shruti , Karuvandan Naveen , Peelay Zoya , Kumar Hemanth , Krishna Madala Ravi , Jadhav Monica , Jalali Rakesh , Patil Vijay Maruti 
Published: June 2022

e14010 Background: Both PCV and Temozolomide (TMZ) are options for adjuvant therapy in grade 2 & grade 3 gliomas after maximal safe resection. The RTOG 9802 PCV regimen is not commonly used as it is perceived as a toxic, poorly tolerated regimen. TMZ is often preferred as it is easy to administer and has fewer adverse events. There has been no head-to-head comparison of these regimens, hence we are conducting a study to compare the 2 regimens. Here, we report the adverse event profile, compliance & quality of life (QoL) of patients enrolled in this study. Methods: This is an ongoing phase 3, non-inferiority trial. Adults with grade 2 glioma with high-risk features (age ≥40 years at diagnosis or residual disease ≥1 cm) or grade 3 gliomas, with ECOG PS 0-2 were enrolled. Patients were randomized 2:1 to receive either adjuvant TMZ or PCV after adjuvant focal conformal radiation (RT). In the TMZ arm patients received RT with concurrent TMZ 75 mg/m2/day (max. 49 days) followed by adjuvant TMZ 150 mg/m2/day on days 1-5 of a 28 day cycle for cycle1, & 200 mg/m2/day cycle 2 onwards (max. 12 cycles).In the PCV arm, patients received Procarbazine 60 mg/m2/day on days 8-21, Lomustine (CCNU) 110 mg/m2 on day 1 & Vincristine (VCR) 1.4 mg/m2 on days 8 & 29 of a 56 day cycle (max. 6 cycles). The primary endpoint of the study is progression-free survival. The current analysis focuses on compliance, adverse events (as per CTCAE v4.03) & QoL (EORTC QLQ C-30 & BN-20). Results: This analysis was limited to the first 50 patients who had completed at least 1 year from the start of adjuvant chemotherapy. There were 32 patients in the TMZ arm & 18 patients in the PCV arm. Two patients each in the TMZ & PCV arms did not start adjuvant chemotherapy. Among those who started adjuvant chemotherapy, the completion rates were higher in the TMZ arm (n = 26,86.7%) as compared to the PCV arm (n = 11,68.8%; p = .241). The median number of cycles of TMZ, Procarbazine, CCNU, and VCR were 12, 5.5, 6 and 5.5 respectively. Dose delays were slightly higher in the PCV arm (81.3%) compared to the TMZ arm (73.3%) which was not statistically significant (p = .722). Chemotherapy dose reductions were needed in 11 patients (68.8%) in the PCV arm & only 1 patient (3.3%) in the TMZ arm, this was statistically significant (p = 0.000). Myelosuppression was significantly higher in the PCV arm as compared to the TMZ arm. The incidence of any grade and grade ≥ 3 anemia, neutropenia & thrombocytopenia was significantly higher with PCV. The incidence of grade 3 lymphopenia was significantly higher with PCV (p = .000). Only 2 patients in the PCV arm developed febrile neutropenia. There was no significant difference in the QoL scores between the two arms at various time points. Conclusions: The use of adjuvant PCV is feasible when administered by experienced neuro-medical oncologists with an acceptable compliance and toxicity profile, without adversely impacting the QoL of patients. Clinical trial information: CTRI/2018/07/015056.