An I.T.M.O. group study on second-line treatment in advanced epithelial ovarian cancer: an attempt to identify clinical and biological factors determining prognosis.
The aim of the present study was to determine the activity of a combined regimen of mitoxantrone (DHAD) and ifosfamide (IFO) and identify clinical and biological factors with prognostic importance for the second-line treatment of ovarian cancer. The following factors were investigated for their prognostic importance: age, disease sites, platinum responsiveness, histological grade, the presence of clinically/radiologically detectable versus not detectable disease, residual disease volume after first surgery, p53 protein, c-erbB-2 oncoprotein and laminin receptor. 72 patients entered the trial. DHAD and IFO therapy led to a 15% response rate among the 47 cases with clinically/radiologically detectable disease (1 complete and 6 partial responses), with a median response duration of 4 months. The response rate was significantly different according to platinum responsiveness (4% objective responses in platinum-resistant versus 27% in platinum-sensitive disease). The time to treatment failure (TTF) and overall survival (OS) were affected by the presence of clinically detectable disease at study entry (median TTF 4 months in the presence of clinically/radiologically detectable disease versus 9 months if the disease was not similarly detectable, P = 0.02; median OS 10 months versus 21 months, P = 0.01). Initially overexpressed in only a few tumours, the c-erbB-2 oncoprotein became overexpressed in 36% of platinum-resistant tumours; this modulation did not occur in platinum-sensitive tumours. Furthermore, laminin receptor was expressed in 77% of platinum-sensitive versus 39% of platinum-resistant patients. There were no differences in p53 protein expression according to drug responsiveness.
Di Leo
A
A
Istituto Nazionale Tumori, Milan, Italy.
Bajetta
E
E
Biganzoli
L
L
Bohm
S
S
Mariani
L
L
Mènard
S
S
Pilotti
S
S
Fabbiani
M
M
Gebbia
V
V
Oriana
S
S
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017671:Platinum Compounds / Q000627:therapeutic use; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012074:Remission Induction; D012307:Risk Factors; D016019:Survival Analysis; D017211:Treatment Failure; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D007069:Ifosfamide; D008942:Mitoxantrone; D017671:Platinum Compounds; D018809:Proliferating Cell Nuclear Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53