A. Martoni

CEA, MCA, CA 15.3 and CA 549 and their combinations in expressing and monitoring metastatic breast cancer: a prospective comparative study

Serum levels of carcinoembryonic antigen (CEA), mucin-like carcinoma-associated antigen (MCA), CA 15.3 and CA 549 were concurrently assayed in patients with metastatic breast cancer. Overall sensitivity in detecting metastatic breast cancer (201 pts) was CEA 45%, MCA 59%, CA 15.3 71% and CA 549 72% (P < 0.01). Sensitivity increased by only 6% to 8% when two or more antigens were simultaneously considered. An overall sensitivity of correlation with objective response (n = 71) was observed in the range of 53-67% (P = n.s.) in patients with abnormal baseline marker values, and in the range of 42-87% (P < 0.05) in patients with normal baseline values. The combination of two or more markers did not improve sensitivity, but decreased specificity of correlation with objective response. In conclusion, CA 15.3 and CA 549 have individually higher sensitivity in detecting metastatic breast cancer. No clinical advantage was observed for using two or more markers concurrently over CA 15.3 or CA 549 alone in the monitoring of metastatic breast cancer.

An Open Randomised Cross-over Study on Granisetron Versus Ondansetron in the Prevention of Acute Emesis Induced by Moderate Dose Cisplatin-containing Regimens*

The aim of the study was to compare granisetron (GRA) with ondansetron (OND) in the prevention of acute emesis in consecutive chemotherapy-naive patients admitted to our department to receive a cytotoxic treatment containing cisplatinum (CP) at a dose > or = 50 mg/m2. Eligible patients were randomised at their first cycle to receive either OND or GRA with cross-over of the anti-emetic treatment on the second cycle. The cytotoxic treatments included five different multidrug regimens containing CP (median dose 60 mg/m2, range 50-70 mg/m2) administered on day 1 and repeated every 21-28 days. OND was administered at the dose of 8 mg x 3 i.v. on day 1 and 8 mg x 2 orally on day 2. GRA was always administered at the dose of 3 mg i.v. on day 1. 124 patients entered the study. 58 patients received OND at their first cycle and 66 received GRA. Complete protection of acute emesis with OND and GRA was observed, with the first and second cycles combined as follows: nausea 53 and 60%, vomiting 68 and 71%, respectively (no statistically significant difference). The cross-over analysis comprising 101 patients confirmed no difference between the two anti-emetic treatments. 21 patients (19%) on OND and 14 patients (12%) on GRA suffered headaches (P = 0.15). 25 (25%) patients preferred OND, 45 (45%) preferred GRA, while 31 (30%) expressed no preference (P = 0.003). However, these differences also depended on the sequence of anti-emetics in the cross-over. In conclusion, in this study, a single dose of GRA is demonstrated to be as effective as multiple doses of OND in the prevention of acute emesis.

Oxaliplatin and protracted continuous 5-fluorouracil infusion in patients with pretreated advanced colorectal carcinoma

BACKGROUNDnBoth OHP and 5-FU are clinically active as single agents in the treatment of metastatic colorectal cancer (MCRC). Clinical and laboratory studies suggest a synergistic interaction between these agents. This phase II study was performed to evaluate the activity of a schedule including OHP and protracted 5-FU infusion in 5-FU-resistant MCRC.nnnPATIENTS AND METHODSnFrom October 1997 to January 2000, 50 patients with measurable progressive MCRC after one or more 5-FU-based regimens were treated. OHP (2-3-hour i.v. infusion) on day 1 and 5-FU (protracted i.v. infusion using elastomeric/electronic pump through a central venous catheter) on days 1-21 were administered every 3 weeks, at the following 4 dose levels: 1) OHP 100 mg/m2 + 5-FU 200 mg/m2 (21 patients); 2) OHP 100 mg/m2 + 5-FU 250 mg/m2 (3 patients); 3) OHP 130 mg/m2 + 5-FU 200 mg/m2 (10 patients); 4) OHP 130 mg/m2 + 5-FU 250 mg/m2 (6 patients).nnnRESULTSnObjective responses were 1 (2%) CR; 10 (20%) PR, for a median duration of 8 months; 23 (46%) stable diseases, for a median duration of 6 months: 16 (32%) progressions. CR + PR was higher in patients who had previously received no more than one line of chemotherapy for metastatic disease as compared with patients who had received two or more lines of therapy (33% vs. 5%, P < 0.01). The median time to progression was four months (one to nine). All dose levels (313 cycles) were well tolerated with mild toxicity. Major toxicity (grade 3 WHO) included: anaemia in 1 patient (2%), nausea and vomiting in 1 patient (2%), diarrhoea in 4 patients (8%) and stomatitis in 1 patient (2%); grade I and 2 peripheral neuropathy were encountered, respectively, in 30 (60%) and 8 (16%) patients. The median survival was 13 months (9-17), with 32 patients still alive after a median follow-up of 8 months.nnnCONCLUSIONSnThis study suggests that 1) OHP plus protracted 5-FU infusion is an active combination in MCRC patients resistant to pre-treatment bolus 5-FU; 2) it has a good tolerability profile and 3) the optimum dose level is OHP 130 mg/m2 and 5-FU 250 mg/m2.

First-line combination chemotherapy with mitoxantrone and cyclophosphamide in advanced breast cancer

SummaryIn this study, 30 evaluable patients with advanced carcinoma of the breast were treated with cyclophosphamide 600 mg/m2 i.v. followed one day later with mitoxantrone (Novantrone®; dihydroxyanthracenedione) 16 mg/m2 i.v. Drug treatment was repeated every 3–4 weeks, for a maximum of 12 cycles. The overall response rate was 43%; five of 30 patients (16%) attained a complete remission, and eight of 30 (27%) had a partial remission. Median response duration was 12+ months. The greater number of responses was seen in skin and soft tissues. Hematologic toxicity was limiting with 75% of patients experiencing substantial-severe leukopenia. Clinically evident heart failure developed in one patient; in three other patients there was minor-moderate alteration of cardiac function during mitoxantrone-cyclophosphamide therapy. Based on these data, it is believed that this regimen may provide significant long-lasting palliation in patients with advanced breast cancer.

523 Tolerability of paglitaxel (Taxol®) in platinum pretreated advanced ovarian cancer patients

Forty-four pts entered this non-randomized phase II study. The pts were treated with TXL (3-hour iv infusion) 175xa0mg/m 2 as second- (nxa0=xa023) or third-line (nxa0=xa013) chemotherapy or with TXL 135xa0mg/m 2 as fourth-line chemotherapy (nxa0=xa08). Standard premedication was required. All the pts are evaluable for toxicity and 35 are evaluable for objective response. An objective remission was observed in 17 (16 PRxa0+xa01 CR)/34 evaluable pts (50%). The median TTP was 28 weeks. The hematological toxicity was mild: grade 3 leukopenia in 8/44 pts (18%); gr. 3 alopecia was universal. Gr. 2–3 paresthesias were observed in 20 pts (45%), while treatment-related pain (abdominal pain, arthralgia, myalgia) was observed in 25 pts (57%). Hypersensitivity reactions occurred in 12 pts (27%); in 2 cases (4%) the reaction was severe (gr. 3 and 4). Partial bowel obstruction occurred within 30 days from TXL administration in 6 pts (14%): the relationship with chemotherapy was uncertain. Overall 8 pts (18%) stopped TXL treatment because of adverse events: 5 hypersensitivity reactions, gr. 3 paresthesias in one case, partial bowel obstruction in 2 cases. In our opinion pts with constipation or bowel subobstructive condition at the beginning of TXL treatment should be carefully selected and monitored.

1254 Predictivity of circulating tumor markers (CEA, MCA, CA 15.3, CA 549) in breast cancer recurrence after surgery

Concomitant measurement of 4 serum markers (CEA, MCA, CA 15.3 and CA 549) were performed every 3–6 months in 128 breast cancer patients with no evidence of disease after surgery. After a median follow-up of 4 yrs (range 3–4 yrs) 29 pts (23%) relapsed. In 24 of these at least one marker was abnormal (sensitivity: 83%); the 5 pts with normal marker value at the time of relapse had only local recurrence (soft tissue metastases). The sensitivity of CEA and MCA (33% and 47%) was significantly lower than the sensitivity of CA 15.3 (79%) and CA 549 (80%) ( P xa0=xa0.02). Ninety-nine pts did not relapse: 90 have normal marker values (specificity: 91%). The predictive value of a positive test and of a negative test is 73% and 95%, respectively. The combination of 2 or more markers does not increase the sensitivity ( P xa0=xa0.7) and the positive predictive value of the test when compared to CA 15.3 or CA 549 alone. In conclusion a single marker determination (CA 15.3 or CA 549) is recommended in the follow-up of pts after surgery for breast cancer.

510 A phase I study of paclitaxel (taxol®) (TXL) and carboplatin (CBDCA) in the treatment of advanced ovarian cancer

An open non-randomized dose finding pilot study was started to evaluate the MTD and the efficacy of the combination TXL-CBDCA. Previously chemotherapy untreated patients with stage III and IV ovarian cancer are eligible for the study. Three patients are required at each dose level and standard criteria are employed to define MTD. TXL is administered as 3-hour iv infusion, followed by CBDCA 30 minutes iv infusion. Premedication with corticosteroids and antihistamines is required. The first dose level was TXL 125xa0mg/m 2 and CBDCA 250xa0mg/m 2 : the dose level progression is done by firstly increasing TXL (25xa0mg/m 2 ) and then CDBCA (50xa0mg/m 2 ). Up to now 9 pts entered the study and the 3rd dose level (TXL 150xa0mg/m 2 ; CBDCA 300xa0mg/m 2 ) has been completed, without reaching the MTD. Twenty-six courses have been administered (15 level I; 7 level II and 4 level III). Gr. 4 toxicities were not observed; gr. 3 alopecia occurred in all pts; gr. 3 neutropenia occurred in 36%, 20% and 50% of courses at dose level I, II and III respectively. No thrombocytopenia occurred. Gr. 2 vomiting was observed in 30% of courses. Advanced results of this study are planned to be available for ECCO 8 meeting.