Abstract | BACKGROUND: Fewer than 20% of patients with bone cancer who are treated with surgery alone are cured. Even with the best current treatment, surgery combined with chemotherapy, only 60%-80% of patients with nonmetastatic bone cancer and 10% of patients with metastatic bone cancer are cured. Thus far, the reason for treatment failure in the nonresponding subset has not been identified. It has been hypothesized that P-glycoprotein, which confers multidrug resistance, might be the cause. We sought to determine whether the expression of P-glycoprotein is associated with poor treatment outcome in osteosarcoma. METHODS: In a retrospective study, we correlated P-glycoprotein expression with the outcome of conventional chemotherapy in 62 consecutive, clinically staged patients diagnosed as having osteosarcoma between 1980 and 1989. RESULTS:
P-glycoprotein was overexpressed in 27 patients but not in another 34 patients, and expression was ambiguous in the sample from one patient. At a median follow-up of 8.9 years, the 34 patients whose tumors did not express P-glycoprotein had significantly better relapse-free rates than the 27 subjects whose tumors expressed the protein (87% versus 0%; P<.00001) and had improved survival rates (94% versus 35%; P<.00001). Among the 46 patients who received chemotherapy before surgery, the 23 whose tumors were negative for P-glycoprotein showed significantly better long-term outcomes (P<.00002), although differences in tumor necrosis in response to therapy were only of borderline significance (P = .057). CONCLUSIONS:
P-glycoprotein expression does correlate with treatment failure in patients with osteosarcoma. This correlation raises the possibility that inhibiting the action of P-glycoprotein as part of therapy for this disease would improve outcome.
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Authors | H S Chan, T M Grogan, G Haddad, G DeBoer, V Ling |
Journal | Journal of the National Cancer Institute
(J Natl Cancer Inst)
Vol. 89
Issue 22
Pg. 1706-15
(Nov 19 1997)
ISSN: 0027-8874 [Print] United States |
PMID | 9390540
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
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Topics |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
(biosynthesis, genetics)
- Adolescent
- Adult
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Bone Neoplasms
(drug therapy, metabolism, surgery)
- Child
- Child, Preschool
- Gene Expression Regulation, Neoplastic
- Humans
- Immunoenzyme Techniques
- Odds Ratio
- Osteosarcoma
(drug therapy, metabolism, surgery)
- Prognosis
- Retrospective Studies
- Treatment Outcome
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