Journal of Clinical Oncology, Vol 4, 46-56, Copyright © 1986 by American Society of Clinical Oncology
Prospective evaluation of carcinoembryonic antigen levels and alternating chemotherapeutic regimens in metastatic breast cancer
CL Loprinzi, DC Tormey, P Rasmussen, G Falkson, TE Davis, HC Falkson and AY Chang
Ninety-seven eligible and evaluable women with metastatic breast cancer
were placed on a prospective clinical protocol to evaluate the use of
continuous cyclic therapy with dibromodulcitol, doxorubicin, vincristine,
tamoxifen, and fluoxymesterone (DAVTH) v DAVTH alternating with
cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP); and
the use of pretreatment and serial carcinoembryonic antigen (CEA) levels in
these patients. Continuous DAVTH and DAVTH/CMFP were equivalent therapies
with respect to response rates, time to treatment failure (TTF), and
survival. Pretreatment CEA levels were elevated (greater than 5 ng/mL) in
42/97 patients and less than 5 ng/mL in the remaining patients. Patients
with elevated pretreatment CEA levels were more likely to be estrogen
receptor (ER) positive (P = .006), to have prolonged disease-free intervals
(P = .017), to have hepatic (P = .004) and/or osseous (P = .01) metastases,
and to have multiple sites of metastatic disease (P = .004). Pretreatment
CEA levels did not significantly predict for overall response rates, TTF,
or survival; nonetheless, those patients with low pretreatment CEA levels
had more complete responses (CRs) (16/55 v 4/42; P = .02). Serial CEA
levels during therapy revealed a number of interesting patterns. During the
first 4 months of treatment, serial CEA levels in responding patients
either (1) progressively declined (15/29 women with elevated pretreatment
CEA levels), or (2) initially rose significantly (mean, 243% of
pretreatment value) and then declined (14/29 women with elevated
pretreatment CEA levels). Peak CEA levels in the latter patients were seen
27 to 135 days following initiation of cytotoxic therapy. In some patients
the initial increase in the CEA level was incorrectly interpreted as
evidence of impending disease progression. CEA levels frequently increased
around the time of clinical disease progression. However, rising CEA levels
rarely provided a clinically meaningful lead time before the appearance of
other clinical evidence of disease progression. These data suggest that
routine pretreatment and monthly serial CEA levels in metastatic breast
cancer patients have minimal use in clinical practice. Two further
noteworthy findings were observed in this prospective study. First,
patients with an unknown ER status had a prolonged median survival when
compared with patients with ER positive or negative tumors; this appeared
to be related to prolonged disease-free intervals in ER unknown patients.
Second, two case of secondary acute leukemia were seen in patients treated
with continuous DAVTH therapy.
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