- Email: [email protected]
Cardiac safety of 3-weekly herceptin monotherapy
Poster Session II. Supportive
number of systemic recurrences in the raloxifen group while no systemic recurrences were observed in the anastrazole group. More specifically, disease free survival rate amounted to 94% in the raloxifen group (6 out of 100 patients relapsed systematically), while the disease free survival rate in the anastazole group was 100%. This difference in disease free survival rate was statistically significant (p-value=0.0294). Conclusion: Taking into account the interim results within 18 months, our feeling was that we should terminate this protocol. However. further studies are required in order to clarify the role of these regiments concerning the above-mentioned issues.
P93 L-J
Polyneuroendocrine therapy of advanced breast cancer with LHRH analogue, tamoxifen and the antiprolactinemic drug cabergoline: Phase 2 study
P. Lissoni, A. Ardizzoia, G. Cerea, M. Acquati. M. Simonelli, M. Vaghi, G. Tancini, G. Gardani. San Gerard0 Hospital, Oncolgia e Radiotempia, Monza - Milano, Italy Despite the well known role of prolactin (PRL) as a growth factor for breast cancer (6C) and the existence of a PRL dependency in estrogen-indipendent tumors, the therapeutic role of the anti-PRL agents for BC is still obscure. This phase-2 study was performed to evaluate efficacy and tolerability of a polyneuroendocrine regimen in heavily pretreated metastatic BC, consisting of Tamoxifen (20 mg/day orally), the LHRH analogue Triptorelin (3.75 mg IM every 28 days) and the long acting antiprolactinemic drug Cabergoline (0.5 mg once/week orally). The study included 14 consecutive patients (pts), 4 of them progressed on Tamoxifen plus LHRH analogue alone. Dominant metastasis sites were, as follows: soft tissues: 4; bone: 4; visceral lesions: 6 (lung: 3; liver: 2; bone marrow: 1). Estrogen receptor (ER) was positive in 5. negative in 3 and unknown in 6 pts. The clinical response consisted of partial response (PR) in 4114 (29%) pts (median duration: 6+ months, range 4-8+), including l/4 (25%) pts, who had a progressive disease (PD) on Tamoxifen plus LHRH alone. Response sites were soft tissues in 1, bone in 2, and visceral lesions in 1. A stable disease (SD) was achieved in 5 other pts (median duration 4+ months), whereas the other 5 pts had a PD. The treatment was extremely well tolerated in all pts, and in particular no cabergolinerelated toxicity occurred. A complete normalization of PRL serum levels was seen in 6/6 pts with abnormally high PRL values prior to therapy. Finally, the treatment induced a significant decline in PRL mean levels, which was significantly higher in pts with PR or SD than in those with PD. This preliminary study shows that the polyneuroendocrine therapy with Tamoxifen, LHRH analogue and Cabergoline is a well tolerated treatment of metastatic BC, which may be effective also in pts with PD on Tamoxifen plus LHRH alone. Therefore, the association of the antiprolactinemic drug Cabergoline may further restore the hormonal dependency of BC.
0P94
Primary chemotherapy in breast cancer shows excellent clinical and pathological response with docetaxel and epirubicin
H.R.C. Marana, J.M. Andrade, D.G. Tiezzi. M.F. Taborda, A.H. Machetti, H.H.A. Carrara, F.J.C. Reis, S. Bighetti. FacultyofMedicine ofRibeirao Preto - lJniverS& Gynecology and Obstetrics - Divion of Oncology: Ribeiro Preto, Bmzil Introduction: Primary chemotherapy is becoming the standard of care for locally advanced breast cancer. New drugs regimens being tested are proving to be more efficacious than the usual anthracycline based treatments. Patients and Methods: Between 04198 and 04101, 56 patients (17 stage IIA; 16 stage IIB, 5 stage IIIA; 18 stage 1118)were included in the trial and received three cycles of docetaxel75 mg/m2 and epirubicin 50 mglm2 (q3w). All patients with stasis or disease progression were excluded from the trial and received alternative treatment. Patients with partial response after three cycles but still not suited for conservative surgery received up to 3 additional cycles. Following completion of the chemotherapy regimen, tumour response was assessed and appropriate surgery performed. Pathological response was assessed in excised specimens. Results: By clinical evaluation according to the UICC criteria, 48 pts (85.7%) had objective regression (6 CR and 42 PR); 7 had stabilisation and 1 showed progression (14.3%). There were no serious complications. Fiftythree patients were eligible for surgery (947%). Of those, 30 were conservative surgery (56.6%) and 23 radical modified surgery (43.4%). Total number of cycles was 184. with an average of 3.28 cycles per patient, which was according to our expectations. Concfusions: Our study demonstrates that docetaxel and epirubicin has a high response rate in locally advanced breast cancer, enabling a high percentage of conservative surgery without significant toxicity.
I P95
cnrdQunlity
of life
S4
I
Cardiac safety of 3-weekly herceptin monotherapy
J. Baselga’, N.-J. Castaneda-Soto*, M. Clemens3, M. Green4, V. Harvey5, S. Morales6, C. Barton?. ‘ HospitalUniversilrio Vat1d’Hebron, Department of Medical 0ncolog)r Barcelona, Spain; 2 lnstituto National de Canceroogia, Tiafpan, Mexico; 3 Mutterhaus o’er Borromaeerihnen, Triec Germany; 4 Royal Melbourne Hospitad Melbourne, Australia; 5 Auckland Hospilal, Auckland, New Zealand; b Hospital Arnau de Villanova, Lleida, Spain; ’ Roche Products L to!, Welwyn Garden City UK An ongoing phase II study (W016229) is evaluating q3-weekly Herceptin monotherapy in women with HERP-positive metastatic breast cancer. The qSweekly regimen is more convenient than the approved weekly schedule and is being used in the ongoing Herceptin Adjuvant (HERA) trial. Safety is a particularly important consideration in patients receiving adjuvant therapy. Here we present interim cardiac safety results. Patients and Methods: 105 patients received Herceptin every 3 weeks by intravenous infusion over 90 minutes, at a dosage of 8mg/kg (first cycle) then Gmgikg (subsequent cycles). 47% of patients had received prior anthracyclines, a risk factor for Herceptin-related cardiotoxicity. Left ventricular ejection fraction (LVEF) was measured by echocardiography or MUGA scan at baseline and after every 4 cycles of treatment. Results: The median LVEF was 63% at baseline and patients had received l-19 (median 5) cycles of treatment at the time of analysis. Among patients with no prior anthracyclines (n=36). 23 (64%) had a decrease in LVEF of .15%. three (8%) had a decrease of 15% or greater and LVEF fell to 150% in two patients (6%). In patients with prior anthracyclines (n=29), LVEF fell by ~15% in 16 (55%). by 15% or greater in five (17%) and to 150% in four (14%). Only one patient (who had received prior anthracycline therapy) developed symptomatic cardiac failure, which resolved after specific therapy. Her LVEF fell from 59% at baseline to 33% at cycle 8. No other serious treatment-related cardiac events were noted. Conclusions: Three-weekly Herceptin monotherapy at a dose of Gmg/kg is associated with a low incidence of symptomatic heart failure in patients with metastatic breast cancer (11%). Asymptomatic LVEF decreases of uncertain significance were noted in a substantial proportion of patients regardless of whether they had received prior anlhracyclines, but reductions of -15% occurred in only a minority of patients. The incidence and severity of cardiotoxicity when Herceptin is given q3-weekly at three times the standard dose was no higher than when it is given in the standard weekly schedule. These results are reassuring for the future of the ongoing HERA trial.
FRIDAY, 14 MARCH 2003
Supportive care/Quality of life
IP96
Undertreatment of anemia in patients with breast cancer (BC): Data from the European Cancer Anaemia Survey (ECUS)
’Universiw Hospital Ghent, Medical Oncology: Gent, Belgium; 2 Veindre NHS TRUST Cardit United Kingdom
S. Van Belle’, PJ. Barrett-Lee’.
Anemia, which causes multiple physical and functional impairments, is one of the most serious side effects of cancer and cancer treatment (tx). ECAS was conducted to establish a comprehensive database to evaluate the prevalence of anemia and the risk factors for development of cancer-related anemia, its impact on World Health Organization (WHO) performance status (PS), and anemia tx practice patterns. Between January and July 2001. 15,367 patients (3278 BC patients) were enrolled at varying times in their tx at 750 cancer centers in 24 European countries and followed for up to 6 months. Data were collected at regularly scheduled visits and included demographics, hemoglobin (Hb) levels, PS, tumor type, cancer tx, and anemia tx. The following are the data for the subset of 3216 BC patients evaluable at enrollment. 67% of BC patients were 160 years old. At enrollment, 57% of BC patients were newly diagnosed (43% of whom were receiving cancer tx). 30% were persistent/recurrent. and 13% were in remission. Cancer tx status at enrollment was: no tx, 54%; radiotherapy (RT), 6%; chemotherapy (CT), 37%; or concomitant CTIRT, 3%. At enrollment. 30% of evaluable BC patients were anemic (Hb 112 g/dL). Respective anemia rates for patients by disease status were: 20% newly diagnosed without cancer tx at enrollment, 34% newly diagnosed with tx, 42% with persistent/recurrent disease, and 23% in remission (P ~0.001); and anemia rates for patients by tx status were: 22% receiving no tx. 43% on CT, 26% on RT, and 37% on CTIRT (P ?? O.OOl). At enrollment, impaired PS with WHO scores of 3 to 4 were recorded for only 2% of patients with Hb r/=12 g/dL vs 8% for patients
number of systemic recurrences in the raloxifen group while no systemic recurrences were observed in the anastrazole group. More specifically, disease free survival rate amounted to 94% in the raloxifen group (6 out of 100 patients relapsed systematically), while the disease free survival rate in the anastazole group was 100%. This difference in disease free survival rate was statistically significant (p-value=0.0294). Conclusion: Taking into account the interim results within 18 months, our feeling was that we should terminate this protocol. However. further studies are required in order to clarify the role of these regiments concerning the above-mentioned issues.
P93 L-J
Polyneuroendocrine therapy of advanced breast cancer with LHRH analogue, tamoxifen and the antiprolactinemic drug cabergoline: Phase 2 study
P. Lissoni, A. Ardizzoia, G. Cerea, M. Acquati. M. Simonelli, M. Vaghi, G. Tancini, G. Gardani. San Gerard0 Hospital, Oncolgia e Radiotempia, Monza - Milano, Italy Despite the well known role of prolactin (PRL) as a growth factor for breast cancer (6C) and the existence of a PRL dependency in estrogen-indipendent tumors, the therapeutic role of the anti-PRL agents for BC is still obscure. This phase-2 study was performed to evaluate efficacy and tolerability of a polyneuroendocrine regimen in heavily pretreated metastatic BC, consisting of Tamoxifen (20 mg/day orally), the LHRH analogue Triptorelin (3.75 mg IM every 28 days) and the long acting antiprolactinemic drug Cabergoline (0.5 mg once/week orally). The study included 14 consecutive patients (pts), 4 of them progressed on Tamoxifen plus LHRH analogue alone. Dominant metastasis sites were, as follows: soft tissues: 4; bone: 4; visceral lesions: 6 (lung: 3; liver: 2; bone marrow: 1). Estrogen receptor (ER) was positive in 5. negative in 3 and unknown in 6 pts. The clinical response consisted of partial response (PR) in 4114 (29%) pts (median duration: 6+ months, range 4-8+), including l/4 (25%) pts, who had a progressive disease (PD) on Tamoxifen plus LHRH alone. Response sites were soft tissues in 1, bone in 2, and visceral lesions in 1. A stable disease (SD) was achieved in 5 other pts (median duration 4+ months), whereas the other 5 pts had a PD. The treatment was extremely well tolerated in all pts, and in particular no cabergolinerelated toxicity occurred. A complete normalization of PRL serum levels was seen in 6/6 pts with abnormally high PRL values prior to therapy. Finally, the treatment induced a significant decline in PRL mean levels, which was significantly higher in pts with PR or SD than in those with PD. This preliminary study shows that the polyneuroendocrine therapy with Tamoxifen, LHRH analogue and Cabergoline is a well tolerated treatment of metastatic BC, which may be effective also in pts with PD on Tamoxifen plus LHRH alone. Therefore, the association of the antiprolactinemic drug Cabergoline may further restore the hormonal dependency of BC.
0P94
Primary chemotherapy in breast cancer shows excellent clinical and pathological response with docetaxel and epirubicin
H.R.C. Marana, J.M. Andrade, D.G. Tiezzi. M.F. Taborda, A.H. Machetti, H.H.A. Carrara, F.J.C. Reis, S. Bighetti. FacultyofMedicine ofRibeirao Preto - lJniverS& Gynecology and Obstetrics - Divion of Oncology: Ribeiro Preto, Bmzil Introduction: Primary chemotherapy is becoming the standard of care for locally advanced breast cancer. New drugs regimens being tested are proving to be more efficacious than the usual anthracycline based treatments. Patients and Methods: Between 04198 and 04101, 56 patients (17 stage IIA; 16 stage IIB, 5 stage IIIA; 18 stage 1118)were included in the trial and received three cycles of docetaxel75 mg/m2 and epirubicin 50 mglm2 (q3w). All patients with stasis or disease progression were excluded from the trial and received alternative treatment. Patients with partial response after three cycles but still not suited for conservative surgery received up to 3 additional cycles. Following completion of the chemotherapy regimen, tumour response was assessed and appropriate surgery performed. Pathological response was assessed in excised specimens. Results: By clinical evaluation according to the UICC criteria, 48 pts (85.7%) had objective regression (6 CR and 42 PR); 7 had stabilisation and 1 showed progression (14.3%). There were no serious complications. Fiftythree patients were eligible for surgery (947%). Of those, 30 were conservative surgery (56.6%) and 23 radical modified surgery (43.4%). Total number of cycles was 184. with an average of 3.28 cycles per patient, which was according to our expectations. Concfusions: Our study demonstrates that docetaxel and epirubicin has a high response rate in locally advanced breast cancer, enabling a high percentage of conservative surgery without significant toxicity.
I P95
cnrdQunlity
of life
S4
I
Cardiac safety of 3-weekly herceptin monotherapy
J. Baselga’, N.-J. Castaneda-Soto*, M. Clemens3, M. Green4, V. Harvey5, S. Morales6, C. Barton?. ‘ HospitalUniversilrio Vat1d’Hebron, Department of Medical 0ncolog)r Barcelona, Spain; 2 lnstituto National de Canceroogia, Tiafpan, Mexico; 3 Mutterhaus o’er Borromaeerihnen, Triec Germany; 4 Royal Melbourne Hospitad Melbourne, Australia; 5 Auckland Hospilal, Auckland, New Zealand; b Hospital Arnau de Villanova, Lleida, Spain; ’ Roche Products L to!, Welwyn Garden City UK An ongoing phase II study (W016229) is evaluating q3-weekly Herceptin monotherapy in women with HERP-positive metastatic breast cancer. The qSweekly regimen is more convenient than the approved weekly schedule and is being used in the ongoing Herceptin Adjuvant (HERA) trial. Safety is a particularly important consideration in patients receiving adjuvant therapy. Here we present interim cardiac safety results. Patients and Methods: 105 patients received Herceptin every 3 weeks by intravenous infusion over 90 minutes, at a dosage of 8mg/kg (first cycle) then Gmgikg (subsequent cycles). 47% of patients had received prior anthracyclines, a risk factor for Herceptin-related cardiotoxicity. Left ventricular ejection fraction (LVEF) was measured by echocardiography or MUGA scan at baseline and after every 4 cycles of treatment. Results: The median LVEF was 63% at baseline and patients had received l-19 (median 5) cycles of treatment at the time of analysis. Among patients with no prior anthracyclines (n=36). 23 (64%) had a decrease in LVEF of .15%. three (8%) had a decrease of 15% or greater and LVEF fell to 150% in two patients (6%). In patients with prior anthracyclines (n=29), LVEF fell by ~15% in 16 (55%). by 15% or greater in five (17%) and to 150% in four (14%). Only one patient (who had received prior anthracycline therapy) developed symptomatic cardiac failure, which resolved after specific therapy. Her LVEF fell from 59% at baseline to 33% at cycle 8. No other serious treatment-related cardiac events were noted. Conclusions: Three-weekly Herceptin monotherapy at a dose of Gmg/kg is associated with a low incidence of symptomatic heart failure in patients with metastatic breast cancer (11%). Asymptomatic LVEF decreases of uncertain significance were noted in a substantial proportion of patients regardless of whether they had received prior anlhracyclines, but reductions of -15% occurred in only a minority of patients. The incidence and severity of cardiotoxicity when Herceptin is given q3-weekly at three times the standard dose was no higher than when it is given in the standard weekly schedule. These results are reassuring for the future of the ongoing HERA trial.
FRIDAY, 14 MARCH 2003
Supportive care/Quality of life
IP96
Undertreatment of anemia in patients with breast cancer (BC): Data from the European Cancer Anaemia Survey (ECUS)
’Universiw Hospital Ghent, Medical Oncology: Gent, Belgium; 2 Veindre NHS TRUST Cardit United Kingdom
S. Van Belle’, PJ. Barrett-Lee’.
Anemia, which causes multiple physical and functional impairments, is one of the most serious side effects of cancer and cancer treatment (tx). ECAS was conducted to establish a comprehensive database to evaluate the prevalence of anemia and the risk factors for development of cancer-related anemia, its impact on World Health Organization (WHO) performance status (PS), and anemia tx practice patterns. Between January and July 2001. 15,367 patients (3278 BC patients) were enrolled at varying times in their tx at 750 cancer centers in 24 European countries and followed for up to 6 months. Data were collected at regularly scheduled visits and included demographics, hemoglobin (Hb) levels, PS, tumor type, cancer tx, and anemia tx. The following are the data for the subset of 3216 BC patients evaluable at enrollment. 67% of BC patients were 160 years old. At enrollment, 57% of BC patients were newly diagnosed (43% of whom were receiving cancer tx). 30% were persistent/recurrent. and 13% were in remission. Cancer tx status at enrollment was: no tx, 54%; radiotherapy (RT), 6%; chemotherapy (CT), 37%; or concomitant CTIRT, 3%. At enrollment. 30% of evaluable BC patients were anemic (Hb 112 g/dL). Respective anemia rates for patients by disease status were: 20% newly diagnosed without cancer tx at enrollment, 34% newly diagnosed with tx, 42% with persistent/recurrent disease, and 23% in remission (P ~0.001); and anemia rates for patients by tx status were: 22% receiving no tx. 43% on CT, 26% on RT, and 37% on CTIRT (P ?? O.OOl). At enrollment, impaired PS with WHO scores of 3 to 4 were recorded for only 2% of patients with Hb r/=12 g/dL vs 8% for patients