Combined pre-operative chemotherapy with intra-arterial cisplatin and continuous intravenous adriamycin for high grade osteosarcoma.
Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment (pre-operative chemotherapy + limb salvage surgery + adjuvant therapy) improved the patients' overall survival and quality of life. We evaluated the efficacy and feasibility of pre-operative chemotherapy with intra-arterial (IA) cisplatin plus continuous intravenous infusion (CI) of adriamycin. We assessed the rate of limb salvage, recurrence pattern and the survival impact based on the histologic response of pre-operative chemotherapy. Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1995. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72 h CI was administered every 3 weeks for 3 cycles, followed by limb salvage surgery if possible or by amputation. According to the histologic tumor response, if the tumor necrosis was >90%, the same regimen was administered for 3 cycles as an adjuvant therapy. A salvage regimen (Ifosfamide 7.5 gm/m2/5 d IV + high dose MTX 10 gm/m2 IV+VP-16 360 mg/m2/3 d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%. Of 41 patients, 37 patients were evaluable for efficacy and toxicities, because 4 patients refused chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 were female with median age of 16 years (range 8-41). The tumor locations were: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (grade III 10; 27.8%, grade IV 17; 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lung. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive cares. Pre-operative chemotherapy with IA DDP+CI ADR followed by surgery showed 75% histologic tumor response rate, 83% limb salvage rate and 54.7% 3-year disease-free survival rate with tolerable side effects. To improve the survival rate, the possible role of good salvage chemotherapy with a non-cross resistance regimen in poor responders should be evaluated.
Rha
S Y
SY
Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-gyu, Seoul, 120-752, Korea.
Chung
H C
HC
Gong
S J
SJ
Shim
K Y
KY
Ahn
J B
JB
Yang
W I
WI
Shin
K H
KH
Yoo
N C
NC
Kim
J H
JH
Roh
J K
JK
Lee
C I
CI
Kim
B S
BS
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005121:Extremities; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D011300:Preoperative Care; D011379:Prognosis; D016879:Salvage Therapy; D012680:Sensitivity and Specificity
D005047:Etoposide; D004317:Doxorubicin; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate