Outcomes with Methotrexate-Free Dyad Chemotherapy in Osteosarcoma Patients: Audit from a Resource-Limited Setting

Abstract Introduction Multiagent chemotherapy forms the backbone for the management of osteosarcoma. The globally accepted chemotherapy regimens for osteosarcoma include a combination of Adriamycin, cisplatin, and high-dose methotrexate (HDMTX). However, non-HDMTX regimens are predominantly used in India, secondary to patient profile, toxicity, administration, logistics, and financial constraints. We present our outcomes with a two-drug dyad chemotherapy consisting of Adriamycin and cisplatin in a resource-limited setting. Objective To determine the disease free and overall survival of osteosarcoma patients and to evaluate the prognostic factors affecting OS for patients with localized disease. Material and Methods The study was a record-based analysis of all osteosarcoma patients presenting at a tertiary care referral center during the period from 2010 to 2019. A total of 127 patients of osteosarcoma were identified, who were evaluated for their demographic and clinical profile, while treatment details and outcomes were evaluated in 123 patients as disease-free survival (DFS) and overall survival (OS). Univariate and multivariate analysis was done for factors influencing OS. Results The median age at presentation was 18 years and extremities were the most common site of presentation. Localized disease (LD) was seen in 102 (80%) patients, while 25 (20%) patients had metastatic disease (MD). Overall, 83 (84%) patients with LD underwent surgery, of whom 65 (78%) underwent limb salvage surgery, while 18 (22%) underwent amputation. Only 72 (73%) patients completed the planned six cycles of chemotherapy. At a median follow-up of 50.4 (range: 1–166.3) months, the 5-year OS for patients with LD and the entire cohort was 53 and 43%, respectively. For patients with MD, the 1- and 2-year OS were 41 and 7%, respectively. The 3- and 5-year DFS for patients with LD was 41 and 35%, respectively. Primary tumor measuring less than 12 cm (p = 0.03) and patients undergoing surgery (p = 0.003) were found to be statistically significant for improved OS on univariate analysis but not on multivariate analysis. Conclusion The two-drug dyad chemotherapy was well tolerated with manageable toxicity. The outcomes were comparable with Indian studies using non-HDMTX regimens that report a 5-year survival of within 50 to 60%, but were inferior to global outcomes and the dose-dense OGS-12 protocol used in India. Raising awareness for early diagnosis, improving the nutritional status, incorporation of sequential third drug (ifosfamide), use of dose-intensive regimens for selected patients, and increasing compliance to treatment may further help improve the outcomes.