Jyoti Bajpai1, Arun Chandrasekharan2, Vijai Simha1, Tanmoy Mandal1, Kajal Shah3, Sachin Hingmare4, Bharath Rangarajan5, Nishitha Shetty6, Tushar Vora1, Jaya Ghosh1, Bharat Rekhi7, Sripad Banavali1, Sudeep Gupta1. 1. Department of Medical Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India. 2. Department of Oncology, Aster Malabar Institute of Medical Sciences, Kozhikode, Kerala, India. 3. Department of Medical Oncology, Shalby Hospital, Ahmedabad, Gujarat, India. 4. Department of Medical Oncology, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India. 5. Department of Medical Oncology, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India. 6. Department of Medical Oncology, Father Muller Medical College, Mangalore, Karnataka, India. 7. Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India.
Abstract
BACKGROUND: The management of osteosarcoma is challenging especially in lower-income and middle-income countries, and there is an unmet need to evolve efficient and sustainable chemotherapy regimens. METHODS: We compared the outcomes in nonmetastatic osteosarcoma patients treated with three sequential non-high-dose methotrexate-based combination chemotherapy protocols at a single tertiary care center over two decades. The first protocol, OGS-99, involved dose-intense, alternating dyads of three drugs: doxorubicin (Dox), cisplatin (CDDP), and ifosfamide (Ifo). The second protocol, OGS-99 enhanced, included OGS-99 drugs with etoposide and enhanced supportive care. The OGS-12 protocol involved dose-dense administration of eight sequential dyads of Dox, CDDP and Ifo, universal growth factor prophylaxis and targeted nutritional support. Event-free survival (EFS), overall survival (OS), and toxicity were reported using a retrospective chart review in the OGS-99 and OGS-99 enhanced protocols and prospectively in the OGS-12 protocol. RESULTS: A total of 41, 94, and 385 treatment-naïve, consecutive, nonmetastatic patients with extremity osteosarcoma were treated with the OGS-99 (2000-2005), OGS-99 enhanced (2010), and OGS-12 (2011-2016), respectively. At a median follow-up of 19, 86, and 39 months, the five-year EFS rates were 38%, 50%, and 62% in the OGS-99, OGS-99 enhanced, and OGS-12, respectively. The corresponding rates of five-year OS were nonevaluable, 60% and 77%, respectively, with acceptable rates of grade 3-4 toxicities: febrile neutropenia (40%), thrombocytopenia (36%), anemia (51%), and 1% deaths related to toxicity. CONCLUSIONS: Sequential selection of an intelligent, dose-dense chemotherapy regimen together with enhanced supportive care resulted in marked improvement in outcomes of nonmetastatic osteosarcoma and this "small steps-big changes" model deserves wider recognition and usage.
BACKGROUND: The management of osteosarcoma is challenging especially in lower-income and middle-income countries, and there is an unmet need to evolve efficient and sustainable chemotherapy regimens. METHODS: We compared the outcomes in nonmetastatic osteosarcomapatients treated with three sequential non-high-dose methotrexate-based combination chemotherapy protocols at a single tertiary care center over two decades. The first protocol, OGS-99, involved dose-intense, alternating dyads of three drugs: doxorubicin (Dox), cisplatin (CDDP), and ifosfamide (Ifo). The second protocol, OGS-99 enhanced, included OGS-99 drugs with etoposide and enhanced supportive care. The OGS-12 protocol involved dose-dense administration of eight sequential dyads of Dox, CDDP and Ifo, universal growth factor prophylaxis and targeted nutritional support. Event-free survival (EFS), overall survival (OS), and toxicity were reported using a retrospective chart review in the OGS-99 and OGS-99 enhanced protocols and prospectively in the OGS-12 protocol. RESULTS: A total of 41, 94, and 385 treatment-naïve, consecutive, nonmetastatic patients with extremity osteosarcoma were treated with the OGS-99 (2000-2005), OGS-99 enhanced (2010), and OGS-12 (2011-2016), respectively. At a median follow-up of 19, 86, and 39 months, the five-year EFS rates were 38%, 50%, and 62% in the OGS-99, OGS-99 enhanced, and OGS-12, respectively. The corresponding rates of five-year OS were nonevaluable, 60% and 77%, respectively, with acceptable rates of grade 3-4 toxicities: febrile neutropenia (40%), thrombocytopenia (36%), anemia (51%), and 1% deaths related to toxicity. CONCLUSIONS: Sequential selection of an intelligent, dose-dense chemotherapy regimen together with enhanced supportive care resulted in marked improvement in outcomes of nonmetastatic osteosarcoma and this "small steps-big changes" model deserves wider recognition and usage.
Authors: Chalinee Monsereenusorn; Ana Patricia Alcasabas; Amos Hong Pheng Loh; Shui Yen Soh; Kenneth Wong Pak Leung; Chetan Dhamne; Sally Blair; Catherine Lam; Piya Rujkijyanont; Chanchai Traivaree; Apichat Photia; Puwadon Veerapan; Mark E Puhaindran; Bernice L Z Oh; Edward Wang; Carlos Rodriguez-Galindo Journal: Asian Pac J Cancer Prev Date: 2022-02-01