Clinical Analysis of Osteosarcoma Patients Treated with High-Dose Methotrexate-Free Neoadjuvant Chemotherapy

Abstract

(1) Objective: High-dose methotrexate (hdmtx) is a common therapeutic agent in the treatment of osteosarcoma. However, hdmtx is highly toxic and requires complex pharmacokinetic monitoring and leucovorin rescue. Thus, alternative therapeutic strategies are necessary. Here, we analyzed the clinical efficacy of a dia regimen (cisplatin–ifosfamide–doxorubicin) to evaluate its potential as an alternative to hdmtx–based therapy. (2) Methods: Patients received 12 cycles of chemotherapy administered over 2 years (2 preoperative cycles and 10 postoperative cycles). Cumulative dose was the same in all cycles: cisplatin 120 mg/m2 on day 1 of week 1, followed by ifosfamide 2.0 g/m2 days 1–5 of week 2, and doxorubicin 20 mg/m2 days 1–3 of week 2. (3) Results: Between January 2004 and October 2008, 39 eligible patients (median age: 16 years) were enrolled, with 36 being evaluable for the study. Of those 36 patients, 20 (55.6%) had a good histologic response to preoperative chemotherapy (>90% tumour necrosis). The estimated 5-year rates of event-free survival (efs) and overall survival were 54.8% and 61.5% respectively. (4) Conclusions: The results of our study suggest that, in osteosarcoma patients, the dia regimen produces an efs rate and survival outcomes comparable to those attained with hdmtx–containing regimens, with fewer adverse reactions. The dia regimen is well tolerated, and we observed a high level of patient compliance. Our results demonstrate that hdmtx-free osteosarcoma treatment regimens can be effective, warranting further investigation.

A study of 853 high grade osteosarcomas from a single institution—Are outcomes in Indian patients different?

“…This adds credence to the possibility that large tumor size in the vast majority of our patients (90% >8 cms; 25% amputation rate) could have impacted on the poorer outcomes . In the current era of limb salvage, assuming amputations to be a surrogate marker for tumor size; Table depicts the outcomes of non‐metastatic patients with high grade osteosarcoma (treated with three drugs or more, with/without methotrexate) in series published within the last 10 years …”

“…Xu et al and Assi et al demonstrated an overall survival of 62% and 69%, respectively in their series without HDMTX . Both these series had limb salvage rates in excess of 90% (possibly a reflection of smaller tumors).…”

“…HDMTX can cause significant toxicities and its administration requires rigorous pharmacokinetic monitoring. Often there are logistic constraints to the use of HDMTX in certain scenarios and effective chemotherapy may be delivered combining the use of various other agents …”

Limb Salvage Surgery for Bone Tumors around the Knee: The Oncological and Functional Outcome—King Hussein Medical Center Experience

“…Chemotherapy has dramatically changed the cure rate of malignant bone tumors [6,[17][18][19]. Since the introduction of effective neo-adjuvant chemotherapy in the 1980s, more than 80% of patients with osteosarcoma of an extremity have been considered candidates for limb-salvage surgery, and that increased the trend of using the endoproshtesis for limb-salvage surgery.…”

“…In the history, before the 1970s, the amputation and knee disarticulation were the main treatment for primary malignant bone tumors around the knee [1,2]. With better understanding of the biological behavior of musculoskeletal tumors, application of effective neo-adjuvant and adjuvant therapy and the development of bone defect reconstruction, 75% of malignant tumors around the knee can be safely resected through some limb salvage procedures [6][7][8][9]. In this paper, we investigate the clinical and functional outcomes of limb salvage operations for bone tumors of the knee.…”