Long-term pulmonary toxicity of multiagent chemotherapy including bleomycin and cyclophosphamide in osteosarcoma survivors.
OBJECTIVE
To assess long-term pulmonary effects of multiagent chemotherapy, we studied serial pulmonary function tests (PFTs) of 35 children with osteosarcoma up to 12 years after diagnosis.


METHODS
We analyzed 84 sets of PFTs from 35 patients diagnosed with osteosarcoma between 1981 and 1991. They received bleomycin, cyclophosphamide, methotrexate, doxorubicin, cisplatin, and actinomycin D over 9-12 months and we performed PFTs from 3 days to 152 months after diagnosis. Time period I included 36 PFTs (43%) performed between 1 and 5 months from diagnosis, time period II included 20 PFTs (24%) performed between 8 and 12 months from diagnosis, and time period III included 28 PFTs (33%) performed between 12 and 119 months from diagnosis. Total lung capacity (TLC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and carbon monoxide diffusing capacity (DLCO) were analyzed. Maximal respiratory pressures and arterial blood gases were measured to assess muscle weakness and gas exchange, respectively. Mean differences in PFTs were compared among the three time periods and between time period pairs.


RESULTS
All mean PFT values showed significant differences among time periods. Significant decline in DLCO; (P=.012), TLC (P=.020), and FEV1 (P=.028) between time periods I and II were noted followed by a trend towards recovery between time periods II and III. Time periods I and III were not significantly different from one another. Mean PFTs performed after 2 years of diagnosis were not different from mean PFTs performed from diagnosis at 2 years.


CONCLUSIONS
This dosage regimen of multi-agent chemotherapy for osteosarcoma patients caused a transient, but significant, decline in PFTs within 8-12 months after administration but appears to cause no significant long-term pulmonary function abnormalities.
Kharasch
V S
VS
Dana Farber Cancer Institute, Boston, Massachusetts, USA.
Lipsitz
S
S
Santis
W
W
Hallowell
J A
JA
Goorin
A
A
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects*; D001859:Bone Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D003609:Dactinomycin / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000187:drug effects*; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D012516:Osteosarcoma / Q000188:drug therapy*; D011653:Pulmonary Diffusing Capacity; D014109:Total Lung Capacity
D001761:Bleomycin; D003609:Dactinomycin; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin; D008727:Methotrexate