Peripheral blood stem cell support reduces the toxicity of intensive chemotherapy for children and adolescents with metastatic sarcomas.
BACKGROUND
To increase the dose intensity (DI) of chemotherapy for pediatric patients with metastatic sarcomas, including the Ewing sarcoma family of tumors (ESFT) and rhabdomyosarcoma (RMS), the authors tested the feasibility of an intensive regimen supported by granulocyte-colony stimulating factor (G-CSF) and peripheral blood stem cells (PBSC).


METHODS
Twenty-three children and adolescents with metastatic sarcomas received vincristine, doxorubicin, cyclophosphamide, ifosfamide, sodium mercaptoethanesulfonate (mensa), and etoposide (VACIME) chemotherapy, consisting of 8 courses of vincristine 2 mg/m(2) on Day 0, doxorubicin 37.5 mg/m(2) per day on Days 0-1, cyclophosphamide 360 mg/m(2) per day on Days 0-4, ifosfamide 1800 mg/m(2) per day on Days 0-4, mesna 2400 mg/m(2) per day, and etoposide 100 mg/m(2) per day on Days 0-4. Doxorubicin was omitted in Courses 7 and 8. G-CSF was given after each course of therapy. Courses of therapy were repeated every 21 days or as soon as hematopoietic recovery permitted. PBSC were collected twice: first, after Course 2 (infused after Courses 3 and 4) and, second, after Course 4 (infused after Courses 5 and 6). Surgical resection followed Course 6, and radiotherapy followed Course 8.


RESULTS
PBSC collections were adequate in 91% of all harvests. The mean DI was 82% (standard deviation, 14%) of the intended DI, which was greater than historic data without PBSC support. Seventeen patients (74%) achieved a complete response (CR), 12 patients with chemotherapy alone and 5 more patients after undergoing surgical resection. Fifteen patients developed progressive disease, with a 2-year event free survival (EFS) rate of 39% (95% confidence interval, 19-59%). Hematopoietic toxicity was severe and cumulative, although it was less than that seen previously without PBSC support.


CONCLUSIONS
PBSC-supported multicycle chemotherapy is a feasible method to increase chemotherapy DI for pediatric patients with metastatic sarcomas. Although the CR rate compared favorably with previously reported response rates, the 2-year EFS rate was similar to that achieved with other intensive regimens.
Hawkins
Douglas S
DS
Department of Pediatrics, Children's Hospital and Regional Medical Center, Seattle, Washington 98105, USA. dhawki@chmc.org
Felgenhauer
Judy
J
Park
Julie
J
Kreissman
Susan
S
Thomson
Blythe
B
Douglas
James
J
Rowley
Scott D
SD
Gooley
Ted
T
Sanders
Jean E
JE
Pendergrass
Thomas W
TW
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects*; D005240:Feasibility Studies; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects*; D007223:Infant; D008297:Male; D015080:Mesna / Q000008:administration & dosage / Q000009:adverse effects*; D009362:Neoplasm Metastasis; D012074:Remission Induction; D012509:Sarcoma / Q000628:therapy*; D012512:Sarcoma, Ewing / Q000628:therapy; D012983:Soft Tissue Neoplasms / Q000628:therapy*; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects*
D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D015080:Mesna; D007069:Ifosfamide