Proffered Papers— Medical Oncology

A PILOT STUDY OF SHORT COURSE, INTENSIVE, MULTIAGENT CHEMOTHERAPY FOR POOR RISK OSTEOSARCOMA

Janinis J, McTiernan A, Cassoni AM, Whelan JS (The London Bone and Soft Tissue Tumour Service, Meyerstein Institute of Oncology, Middlesex Hospital, London W1N 8AA, UK)

Aim: To assess the feasibility, toxicity and response to short course, multiagent chemotherapy culminating in peripheral stem cell supported high-dose chemotherapy(HDC) in patients with poor risk osteosarcoma(OS)

Patients And Methods: Between April 1995 and April 1999 30 patients entered the study. Median age: 24 years (range 9-46). Median age for extremity OS: 17 years and for pelvic/axial OS: 30 years. Male to female ratio 1.7:1. Primary site: Extremity OS 14, Pelvic OS 12, Other 4. Metastases at presentation: 15/30. Chemotherapy consisted of 5 blocks given consecutively. Block 1: cisplatin 100 mg/m₂, doxorubicin 75 mg/₂ q 14 days x2. Block 2 (x1): cisplatin 50 mg/m2, ifosfamide 4 gr/m₂, and etoposide 500 mg/m₂ (stem cell harvest post Block 2). Block 3: ifosfamide 18 gr/m₂ q 21 days x 2. Block 4: methotrexate 12 g/m₂ q 7-10 days x 3. Block 5 (administered around week 21): carboplatin AUC8, and etoposide 400 mg/m₂ on days -8, -6, and -4, cyclophosphamide 60 mg/kg on days -6 and -4. On day 0 patients underwent reinfusion of their harvested stem cells.

Results: A total of 226 cycles of chemotherapy (blocks 1-5) were administered. A significantly higher number of patients with extremity OS received more than 75% of the intended dose of chemotherapy or the intended number of cycles for Blocks 2, 3, and 4 compared to those with pelvic/axial OS. HDC was administered to 11 patients (10 with extremity OS and one with a pelvic OS). Grade 3 or 4 toxicity (Blocks 1-4): neutropenia 49 % of cycles, thrombocytopenia 26%. There were 59 episodes of febrile neutropenia. There were two treatment related deaths: one post HDC from sepsis, and one during surgery. Responses:(30 patients evaluable) PR:30%, mR:17%, SD:47%, PD: 6%. Histologic response (22/26 evaluable patients) >90% tumor necrosis: 23%. Twenty seven patients underwent primary surgery. Limb salvage operation: 20. Eight patients underwent pulmonary metastasectomy. The median survival time for the whole group was 16 months (95% CI:13 to 19 months). The 2-year survival rate for the whole group of patients was 33 % (50% for extremity tumors and 19% for pelvic/axial tumors), median follow up: 16 months (range 7-57).

Conclusion: Dose intensive multiagent chemotherapy is feasible in the group of patients with extremity OS but not those with pelvic/axial primaries. A number of factors may account for this such as higher age group and poor performance status. Inferior survival rates in the pelvic/axial group are attributed to poor local tumor control by surgery and less dose intensive treatment.