Enhancement of the efficacy of weekly low-dose taxotere by the long acting anti-prolactinemic drug cabergoline in pretreated metastatic breast cancer.
In view of its potential action as a growth factor, the evidence of abnormally high blood levels of prolactin (PRL) is associated with a poor prognosis in metastatic breast cancer. Moreover, metastatic breast cancer-related hyperprolactinemia has proven to counteract the efficacy of cancer chemotherapy. The negative influence of high blood levels of PRL on the efficacy of chemotherapy in metastatic breast cancer has been confirmed by previous preliminary studies, showing that the concomitant administration of the anti-prolactinemic dopaminergic agent bromocriptine may enhance the therapeutic effect of chemotherapy. However, the clinical use of bromocriptine is limited by its short duration and gastrointestinal toxicity. Therefore, new anti-prolactinemic drugs, characterized by less toxicity and a longer duration of activity, such as Cabergoline (CBG), could be more appropriated to control PRL secretion in breast cancer. On this basis, a study was planned to evaluate the efficacy and tolerability of a concomitant administration of CBG with weekly low-dose Taxotere (TXT) in pretreated metastatic breast cancer under chemotherapy. The study group comprised 70 metastatic breast cancer patients (females), pretreated with at least one previous chemotherapeutic line containing anthracyclines, who were randomized to be treated with TXT alone or TXT plus CBG. TXT 25 mg/m2 was given i.v. at weekly intervals for at least 9 consecutive cycles. CBG was given orally at 0.5 mg once per week. Abnormally high pre-treatment levels of PRL were seen in 24/70 (34%) patients, 11 of whom were treated with TXT plus CBG, whereas the other 13 received TXT alone. CBG induced a complete normalization of the PRL levels in all patients within the first two weeks of therapy, whereas no normalization of PRL occurred spontaneously in patients treated with chemotherapy alone. The objective tumor regression rate was significantly higher in patients concomitantly treated with CBG than in those who received chemotherapy alone (31/34 vs 13/36, p < 0.05), and this difference was particularly evident in patients with high PRL levels prior to therapy (6/11 vs 2/13). No CBG-related toxicity occurred. On the contrary, chemotherapy-induced asthenia was significantly lower in patients concomitantly treated with CBG (5/34 vs 11/36, p < 0.05). This study shows that the chemoneuroendocrine therapy of weekly low-dose TXT plus the anti-prolactinemic drug CBG is a new, effective and well-tolerated therapy for metastatic breast cancer. It may also be recommended in heavily pretreated patients or in those with poor clinical status.
Frontini
L
L
Division of Radiation Oncology, San Gerardo Hospital, Monza, Milan, Italy.
Lissoni
P
P
Vaghi
M
M
Perego
M S
MS
Pescia
S
S
Ardizzoia
A
A
Gardani
G
G
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D000077465:Cabergoline; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004873:Ergolines / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D011388:Prolactin / Q000097:blood; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
D004873:Ergolines; D043823:Taxoids; D000077143:Docetaxel; D011388:Prolactin; D000077465:Cabergoline