Jyoti Bajpai1, Arun Chandrasekharan2, Vikas Talreja3, Vijai Simha4, M V Chandrakanth5, Bharat Rekhi6, Sachin Khurana7, Arif Khan8, Tushar Vora9, Jaya Ghosh10, Shripad D Banavali11, Sudeep Gupta12. 1. Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, 400 012, India. Electronic address: dr_jyotibajpai@yahoo.co.in. 2. Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, 400 012, India. Electronic address: groundhogcs@gmail.com. 3. Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, 400 012, India. Electronic address: vikasttalreja@gmail.com. 4. Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, 400 012, India. Electronic address: vijaiaditya1985@gmail.com. 5. Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, 400 012, India. Electronic address: drmvch@gmail.com. 6. Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, 400 012, India. Electronic address: rekhi.bharat@gmail.com. 7. Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, 400 012, India. Electronic address: dr.sachinkhurana@gmail.com. 8. Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, 400 012, India. Electronic address: khandrarif1981@gmail.com. 9. Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, 400 012, India. Electronic address: tusharsvora@yahoo.com. 10. Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, 400 012, India. Electronic address: archana_jaya_ghosh@yahoo.co.in. 11. Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, 400 012, India. Electronic address: banavali_2000@yahoo.com. 12. Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, 400 012, India. Electronic address: sudeepgupta04@yahoo.com.
Abstract
PURPOSE: High-dose methotrexate (HDMTX)-based regimens are widely used in osteosarcoma. However, mandatory in-patient treatment with complex pharmacokinetic monitoring requirement precludes its use, especially in resource-constrained settings of low- and middle-income countries (LMICs). METHODS: All treatment naive consecutive patients of osteosarcoma were prospectively treated on a novel institutional regimen (named OGS-12) comprising of eight sequential doublets of the following drugs: doxorubicin, cisplatin and ifosfamide in four courses each, given in the neoadjuvant and adjuvant settings. Data were prospectively collected on baseline characteristics, histological response to neoadjuvant chemotherapy (NACT), toxicity, event-free survival (EFS) and overall survival (OS). RESULTS: Between 2011 and 2014, 317 treatment naive patients with extremity osteosarcoma were seen, of whom 237 (75%) were non-metastatic. Majority had high tumour burden, with mean tumour size of 10.45 cm, high serum lactate dehydrogenase (LDH) and serum alkaline phosphatase (SAP) in 71% and 88% respectively. A significant number (34%) were nutritionally challenged. Two-hundred ten of 237 patients were analysable for histological response of which 58% had good response (viable cells ≤10%). At the median follow-up of 34.31 (2-60) months, in intention-to-treat (ITT) analysis, the 5-year EFS and OS were 56% and 75% respectively; the same were 60% and 80% in per-protocol analysis. There was febrile neutropenia (FN) in 56%, grade 3/4 thrombocytopaenia in 22% and anaemia in 47% with two chemotoxic deaths. Ten percent of the patients had grade 3/4 diarrhoea and stomatitis and one patient developed grade 4 acute kidney injury requiring dialysis. Baseline SAP (per-protocol) for EFS and performance status (ITT) for OS were found to be independent variables. Histological response was an independent predictor for EFS and OS in both the analyses. CONCLUSIONS: In treatment naive patients with non-metastatic osteosarcoma, OGS-12 protocol, a dose-dense, non-HDMTX-based, novel, economic and easy to administer regimen produces comparable outcomes to international standards, with acceptable toxicity and is worthy of wider clinical application.
PURPOSE: High-dose methotrexate (HDMTX)-based regimens are widely used in osteosarcoma. However, mandatory in-patient treatment with complex pharmacokinetic monitoring requirement precludes its use, especially in resource-constrained settings of low- and middle-income countries (LMICs). METHODS: All treatment naive consecutive patients of osteosarcoma were prospectively treated on a novel institutional regimen (named OGS-12) comprising of eight sequential doublets of the following drugs: doxorubicin, cisplatin and ifosfamide in four courses each, given in the neoadjuvant and adjuvant settings. Data were prospectively collected on baseline characteristics, histological response to neoadjuvant chemotherapy (NACT), toxicity, event-free survival (EFS) and overall survival (OS). RESULTS: Between 2011 and 2014, 317 treatment naive patients with extremity osteosarcoma were seen, of whom 237 (75%) were non-metastatic. Majority had high tumour burden, with mean tumour size of 10.45 cm, high serum lactate dehydrogenase (LDH) and serum alkaline phosphatase (SAP) in 71% and 88% respectively. A significant number (34%) were nutritionally challenged. Two-hundred ten of 237 patients were analysable for histological response of which 58% had good response (viable cells ≤10%). At the median follow-up of 34.31 (2-60) months, in intention-to-treat (ITT) analysis, the 5-year EFS and OS were 56% and 75% respectively; the same were 60% and 80% in per-protocol analysis. There was febrile neutropenia (FN) in 56%, grade 3/4 thrombocytopaenia in 22% and anaemia in 47% with two chemotoxic deaths. Ten percent of the patients had grade 3/4 diarrhoea and stomatitis and one patient developed grade 4 acute kidney injury requiring dialysis. Baseline SAP (per-protocol) for EFS and performance status (ITT) for OS were found to be independent variables. Histological response was an independent predictor for EFS and OS in both the analyses. CONCLUSIONS: In treatment naive patients with non-metastatic osteosarcoma, OGS-12 protocol, a dose-dense, non-HDMTX-based, novel, economic and easy to administer regimen produces comparable outcomes to international standards, with acceptable toxicity and is worthy of wider clinical application.
Authors: Marina Curra; Amanda F Gabriel; Maria Beatriz C Ferreira; Marco Antonio T Martins; André T Brunetto; Lauro J Gregianin; Manoela Domingues Martins Journal: Support Care Cancer Date: 2021-04-12 Impact factor: 3.603
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