Randomized, double-blind, multicenter trial comparing clinafloxacin with imipenem as empirical monotherapy for febrile granulocytopenic patients.

In a double-blind, multicenter trial, 541 febrile granulocytopenic patients were randomized to receive either intravenous (iv) clinafloxacin (200 mg every 12 h) or i.v. imipenem (500 mg every 6 h) as empirical monotherapy. More baseline pathogens were susceptible to clinafloxacin (259 [99%] of 262 organisms) than to imipenem (253 [95%] of 265; P=.03). Initial favorable clinical response rates for clinafloxacin (88 [32%] of 272 patients) and imipenem (89 [33%] of 269) were similar. After addition of other antimicrobial agents, overall response rates were 259 (95%) of 272 for clinafloxacin and 251 (93%) of 269 for imipenem. During the study, only 13 clinafloxacin (5%) and 18 imipenem (7%) recipients died. Both drugs were generally well tolerated. Drug-related skin rash occurred more often with clinafloxacin (11% vs. 6%; P=.07), whereas nausea (2% vs. 5%; P=.16), Clostridium-difficile-associated diarrhea (3% vs. 8%; P=.02), and seizures (0% vs. 2%; P=.06) occurred more often with imipenem. These results suggest that clinafloxacin and imipenem have similar efficacy as empirical monotherapy in febrile granulocytopenic patients.

High-dose chemotherapy for high-risk primary breast cancer: an on-site review of the Bezwoda study.

BACKGROUND: The efficacy of high-dose chemotherapy with progenitor-cell rescue for women with breast cancer is a controversial issue. Although historically controlled trials have suggested a survival advantage for high-dose chemotherapy, several randomised studies have yet to confirm this advantage. Two studies, however, by Bezwoda, of patients with high-risk and metastatic disease, seemed to show a significant survival advantage for high-dose compared with conventional-dose chemotherapy for metastatic and high-risk primary breast cancer. METHODS: To corroborate the study results before starting a large international confirmatory study, a US team did an on-site review of records for patients in the high-risk study. Limited numbers of records were made available for review, all of which were for patients who received the high-dose-chemotherapy regimen. FINDINGS: There was much disparity between the reviewed records and the data presented at two international meetings. In addition, the reviewers saw no signed informed consent, and the institutional review committee had no record of approval for the investigational therapy. After the site visit, Bezwoda admitted scientific misconduct by using a different control chemotherapy regimen from that described in presented data. INTERPRETATION: The Bezwoda study should not be used as the basis for further trials to test the efficacy of the cyclophosphamide, mitoxantrone, etoposide regimen for high-dose chemotherapy in women with high-risk primary breast cancer. This review validates the essential nature of on-site audits, especially in single-institution studies.

Review of clinical studies of CA 27.29 in breast cancer management.

A critical review of CA 27.29 and CA 15-3 is performed in this paper. A review of the literature is undertaken. A review of the FDA submissions for 27.29 for both early stage and monitoring metastatic breast cancer patients is reviewed.

A comparison of efficacy of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in the therapeutic setting of chemotherapy-induced myelosuppression.

A randomized, double-blind, multicenter study in 181 afebrile cancer patients with ANC levels < 500/microL receiving myelosuppressive chemotherapy was undertaken to compare sargramostim (yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor, RhuGM-CSF) and filgrastim (bacteria-derived recombinant human granulocyte colony-stimulating factor, RhuG-CSF) in the treatment of chemotherapy-induced myelosuppression. Patients received daily subcutaneous (SC) injections of either agent until ANC levels reached at least 1500/microL. There was no statistical difference between treatment groups in the mean number of days to reach an ANC of 500/microL, but the mean number of days to reach ANC levels of 1000/microL and 1500/microL was approximately one day less in patients receiving filgrastim. Fewer patients in the sargramostim arm were hospitalized, and they had a shorter mean length of hospitalization, mean duration of fever, and mean duration of i.v. antibiotic therapy compared with patients who received filgrastim. Both growth factors were well tolerated. No patient was readmitted to the hospital after growth factor was discontinued. Sargramostim and filgrastim have comparable efficacy and tolerability in the treatment of standard-dose chemotherapy-induced myelosuppression in community practice.

Randomized trial comparing the tolerability of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in cancer patients receiving myelosuppressive chemotherapy.

A prospective, randomized, double-blind, multicenter study in cancer patients receiving myelosuppressive chemotherapy was undertaken to evaluate and compare the tolerability of sargramostim (yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor, RhuGM-CSF) and filgrastim (bacteria-derived recombinant human granulocyte colony-stimulating factor, RhuG-CSF) in the prophylaxis or treatment of chemotherapy-induced neutropenia. In all, 137 evaluable patients received sargramostim (300 micrograms; 193 mg/m2) or filgrastim (481 mg; 7 mg/kg) once daily by self-administered s.c. injection, usually beginning within 48 h after completion of chemotherapy. With the exception of a slightly higher incidence of grade 1 fever (< 38.1 degrees C) with sargramostim, there were no statistically significant differences in the incidence or severity of local or systemic adverse events possibly related to the growth factors. Although the study was not designed to evaluate efficacy directly, there also were no statistically significant differences between treatment groups in total days of growth factor therapy, days of hospitalization, or days of i.v. antibiotic therapy during the treatment period. Both sargramostim and filgrastim were comparably well tolerated when given by s.c. injection in this group of patients, and no clinically significant differences between the growth factors were demonstrated.

Use of Truquant BR radioimmunoassay for early detection of breast cancer recurrence in patients with stage II and stage III disease.

PURPOSE: The Truquant BR radioimmunoassay (RIA) (Biomira Diagnostics Inc, Rexdale, Canada) uses the monoclonal antibody B27.29 to quantitate the MUC-1 gene product (CA 27.29 antigen) in serum. We evaluated CA 27.29 antigen in a controlled, prospective clinical trial for its ability to predict relapse in stage II and stage III breast cancer patients. PATIENTS AND METHODS: Over a 2-year period, 166 patients who had completed therapy for stage II (80.1%) or III (19.9%) breast cancer and were clinically free of disease were serially tested for CA 27.29 antigen levels. The study was double-masked and cancer recurrence was documented based on clinical findings. Patients with two consecutive CA 27.29 antigen test results above the upper limit of normal were considered positive. RESULTS: The Truquant BR RIA had a sensitivity of 57.7%, specificity of 97.9%, positive predictive value of 83.3%, and negative predictive value of 92.6%. The recurrence rate was 15.7%. A Cox regression analysis showed that the only variable to correlate with recurrent disease was the CA 27.29 antigen test result. Patients with a positive test result had increased odds of having a recurrence (odds ratio, 6.8; P < .00001). The test was effective in predicting recurrence in patients with both distant and locoregional disease. In a subgroup of patients with bone pain, CA 27.29 antigen level was found to identify reliably patients who would subsequently develop recurrent disease. CONCLUSION: These data demonstrate that the Truquant BR RIA can be used as an aid to predict recurrent breast cancer in patients with stage II and III disease.

Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein versus granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for non-Hodgkin's lymphoma: results of a randomized double-blind trial.

PURPOSE: A phase III trial to compare PIXY321 with granulocyte-macrophage colony-stimulating factor (GM-CSF) following high-dose therapy and autologous bone marrow transplant (ABMT) was conducted to evaluate the time to hematopoietic recovery. PATIENTS AND METHODS: One hundred seventy-seven patients with non-Hodgkin's lymphoma (NHL) receiving ABMT were randomized to receive either PIXY321 750 micrograms/m2/d divided into two subcutaneous (SC) doses or GM-CSF 250 micrograms/m2/d as a 2-hour intravenous (IV) infusion starting on day 0 post-ABMT for a maximum of 28 days. RESULTS: The median time to reach an absolute neutrophil count (ANC) > or = 500/microL in the PIXY321 group was 17 days versus 19 days in the GM-CSF group (P = .07) and the median time to reach platelet transfusion independence in the PIXY321 group was 25 days versus 23 days in the GM-CSF group (P = .30). The toxicity profiles of the two agents appeared to be equivalent with the exception of more patients in the PIXY321 group with a rash (64%) compared with the GM-CSF group (48%) (P = .028). A logistic regression model identified the use of a non-total-body irradiation (TBI) regimen and/or receipt of unpurged marrow and a body-surface area greater than 2.0 m2 as predictive of faster neutrophil engraftment, and those three factors, as well as the receipt of < or = two prior chemotherapy regimens as predictive for rapid platelet engraftment. CONCLUSION: There was a trend toward a slight improvement in neutrophil engraftment post-ABMT with the PIXY321 administered by an SC route compared with GM-CSF administered by an IV route. However, no differences could be identified between the two agents with respect to the time to platelet transfusion independence. Patient, regimen, and graft characteristics were most predictive of the engraftment tempo.

A phase II trial of autologous bone marrow transplantation (ABMT) in acute leukemia with edelfosine purged bone marrow.

Alkyl-lysophospholipid compounds which are selectively cytotoxic to neoplastic cells and relatively sparing of normal marrow progenitor cells are appealing as purging agents to rid remission marrows of residual leukemic cells. A multi-institutional phase II study was conducted in 57 patients with acute leukemia (50 AML and 7 ALL) in which remission marrows were purged in vitro and reinfused after ablative chemotherapy. The median time for granulocyte recovery to 500/microliter was 33 days and for platelet recovery to 25000/microliter was 46 days. The overall DFS and survival was 37% and 46% respectively. Transplantation in first remission gave a better survival than transplant in a subsequent remission.

Management of recurrent breast cancer.

A major challenge for the clinician in treating patients with metastatic breast cancer is to achieve the best tumor response with the least toxicity. A number of different clinical situations present, and several options for interventions are available. In addition, patients with metastatic disease are candidates for newer approaches. Currently, intensive chemotherapy with the potential goal of cure has been enthusiastically received; however, in most patients, the goal is palliation. Achieving this goal requires an understanding of the natural history of breast cancer and of the patient and her needs.

Breast cancer marker Ca549. A multicenter study.

A multicenter study of CA549, a marker for breast cancer, was conducted using sera from 1721 patients with benign and malignant conditions by an immunoradiometric assay, BRESMARQ. Acceptable assay performance was demonstrated by studies of intra-assay (2.2% to 12% coefficient of variation [CV]), interassay (4.1% to 11.8% CV), and interlaboratory (4.8% to 8.7% CV) precision; sensitivity (.3 kU/L); linearity; recovery; high-dose hook effect (up to 10,000 kU/L); and interferences (human antimouse antibodies; protein, bilirubin, hemoglobin levels; lipid and cancer therapeutic agents). A reference interval of 0-12.5 kU/L (women) and 0-11.9 kU/L (men) was established from 746 healthy persons. The distribution of values exceeding the reference range for benign conditions was as follows: pregnant and lactating women (2%); benign breast disease (5%); and seven other benign diseases, including liver (24%), lung (19%), prostate (14%), colon, endometrial, gastric, and ovarian (< 10%). For nonbreast cancers, the distribution was Hodgkin's (7%), colon (10%), endometrial (15%), gastric (15%), lymphoma (15%), prostate (20%), ovarian (39%), and liver (45%). For breast cancer, the distribution was stage I (5%), stage II (14%), stage III (32%), and stage IV (74%). The receiver-operating characteristic analysis demonstrated the usefulness of CA549 as a marker in stage IV breast cancer.

Marijuana as an antiemetic drug: how useful is it today? Opinions from clinical oncologists.

OBJECTIVE: To determine the antiemetic drug preferences of practicing adult oncologists and to estimate the frequency of use of marijuana smoke as an antiemetic agent. DESIGN: Identical mailed questionnaire surveys on antiemetic preferences, distributed prior to approval of ondansetron. SAMPLE: Two groups of practicing clinical adult oncologists were surveyed. The first group (N = 120) consisted of every twentieth board-certified, American member of the American Society of Clinic Oncology culled from the 1990 ASCO membership directory in alphabetical order. The second group (N = 60) consisted of every adult clinical oncologist in metropolitan Washington, D.C. MEASUREMENTS/RESULTS: Completed surveys were returned by 141 (78%) physicians; the responses from both groups were almost identical (Wilcoxon Rank Sum Test). Marijuana (either as marijuana smoke or oral tetrahydrocannabinol) ranked ninth in order of preference for the treatment of mild to moderate nausea and vomiting, and sixth for the treatment of more severe symptoms induced by chemotherapy. Most (94 or 65%) respondents reported having prescribed marijuana or oral THC 10 times or less; only 5 (3.5%) had prescribed such drugs more than 100 times which represented for them about 1% of their average lifetime clinical patient load. The respondents who had prescribed marijuana in any form thought that it had effectively relieved post-chemotherapy nausea or vomiting in 50% of patients. Unpleasant adverse effects were estimated to have occurred in 25% of treated patients. Only 8 (6%) respondents indicated that they would prescribe marijuana much more frequently--if there were no legal barriers associated with its medical use. CONCLUSION: Marijuana in any form was believed to be efficacious for 50% of patients with pre- or post-chemotherapy nausea or vomiting. However, one of four patients who received it complained of bothersome adverse effects. At the time of the study, cannabis was prescribed or recommended relatively infrequently by American clinical oncologists (i.e., those who actually prescribed chemotherapy). Even if it was freely available and restrictions on its use liberalized, smokeable marijuana, according to responses given on this survey, would not be used much more frequently by American oncologists.

Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma.

PURPOSE: To test the activity of a regimen of interferon alfa-2a (IFN alpha-2a) 5 x 10(6) U/m2 subcutaneously (SC) days 1 through 7 combined with leucovorin 500 mg/m2/d intravenously (IV) over 30 minutes and fluorouracil (5-FU) 370 mg/m2/d through IV push 1 hour after leucovorin days 2 through 6 in a phase II study. PATIENTS AND METHODS: Forty-six patients with a good performance status (PS) with measurable colorectal cancer and no prior therapy for metastatic disease were entered. Cycles were repeated at 3-week intervals if toxicity had resolved. The 5-FU dose was increased by 15% if toxicity was mild, and decreased by 15% for grade 3 to 4 nonhematologic or grade 4 hematologic toxicity. RESULTS: Three complete responses (CRs) and 21 partial responses (PRs) were seen among 44 assessable patients (54%; 95% confidence interval, 39% to 70%). A moderately strong association was noted between PS and response: PS O (n = 26), two CRs and 15 PRs (65%); PS 1 (n = 13), one CR and six PRs (54%); PS 2 (n = 5), zero CRs and zero PRs (0%; two-tailed P = .026). With a median follow-up duration of 18.8 months, the median time to treatment failure (TTF) and survival were 7.8 months and 16.3 months, respectively. Doses were escalated to 425 mg/m2/d 5-FU in 10 patients, but only four tolerated the higher dose. When expressed as the most severe degree of toxicity experienced by each patient across all cycles, grade 3 to 4 toxicity of the following types was observed; mucositis, 37%; diarrhea, 40%; rash, 7%; fatigue, 14%; granulocytopenia, 13%. Dose-limiting toxicity at 370 mg/m2/d 5-FU eventually occurred in 28 patients (61%). Twelve patients (26%) required an IFN alpha-2a dose reduction for constitutional toxicity. CONCLUSION: This regimen has promising activity in advanced colorectal cancer, particularly in patients with an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1.

Efficacy and tolerability of imipenem-cilastatin versus ceftazidime plus tobramycin as empiric therapy of presumed bacterial infection in neutropenic cancer patients.

The efficacy and tolerability of monotherapy with imipenem-cilastatin (I-C) were compared with that of ceftazidime plus full-course therapy with an aminoglycoside (tobramycin) (C&T) in the treatment of presumed bacterial infection in neutropenic cancer patients. A total of 106 adult patients diagnosed with presumed bacterial infection and an underlying malignancy with an absolute neutrophil count (ANC) < 500/mm3 were enrolled in this open-label study. A total of 131 febrile episodes occurred. Forty-five patients in the I-C group and 41 in the C&T group, who were well matched on demographic and baseline characteristics, were evaluable for efficacy and safety. Seventy-two hours after the start of therapy, no significant between-group differences in treatment outcomes, including withdrawals or deaths, were seen. Thirty-five (78%) of 45 patients in the I-C group and 29 (71%) of the 41 in the C&T group had successful outcomes at the final evaluation. Superinfection occurred in 8 (18%) I-C patients and 3 (7%) C&T patients. Within the subgroup of patients with an initial ANC < 100/mm3, the final evaluation showed no significant differences in treatment outcome between groups. Of the 131 in the safety population 30 (46%) I-C patients and 28 (42%) C&T patients had one or more adverse experiences; drug-related adverse events occurred in 25 (38%) patients in the I-C group and 11 (17%) patients in the C&T group. The data suggest that imipenem-cilastatin should be considered for initial empiric therapy of presumed bacterial infection in neutropenic cancer patients.

Phase I trial of intravenous cyclosporine to induce graft-versus-host disease in women undergoing autologous bone marrow transplantation for breast cancer.

PURPOSE: We investigated if graft-versus-host disease (GVHD), which is associated with an antitumor effect, could be induced in women with advanced breast cancer by treatment with cyclosporine (CSA) following reinfusion of purged autologous marrow after treatment with high-dose chemotherapy and defined the toxicities of this approach. PATIENTS AND METHODS: Fifty-one women with advanced breast cancer responding to therapy were treated with escalating doses of CSA (1.0, 2.5, or 3.75 mg/kg/d) for 28 days following high-dose chemotherapy and autologous bone marrow transplantation and monitored for induction of GVHD and toxicity of therapy. RESULTS: GVHD was induced in a dose-dependent fashion in 14%, 68%, and 92% of patients at each dose level, respectively, a median of 15 days following autologous marrow reinfusion. GVHD was clinically mild and limited to skin. Toxicity was acceptable, with two deaths within 50 days of marrow reinfusion. Statistically significant increases in maximum creatinine and bilirubin levels were seen at all dose levels when compared with similarly treated historic controls who did not receive CSA. Time to last platelet transfusion was significantly delayed in patients treated at the highest dose. CONCLUSION: GVHD can be safely induced by treatment with CSA in women with advanced breast cancer who are receiving high-dose alkylating agents and autologous bone marrow transplantation. The toxicity of this approach is acceptable. Evidence of antitumor efficacy awaits further investigation.

High-dose chemotherapy with reinfusion of purged autologous bone marrow following dose-intense induction as initial therapy for metastatic breast cancer.

We assessed the toxicity and efficacy of high-dose chemotherapy consolidation with reinfusion of purged autologous bone marrow in women with metastatic breast cancer responding to a dose-intense outpatient regimen. Thirty women with hormone-unresponsive metastatic breast cancer, previously untreated with adjuvant doxorubicin or with any chemotherapy for metastatic disease, were treated with cyclophosphamide, methotrexate, doxorubicin, fluorouracil, vincristine, and leucovorin for 16 weeks. Twenty-four patients responded to therapy; 8 showed a complete response, and 16 showed a partial response. These patients proceeded to the next phase of the protocol, ie, marrow harvest and treatment with 6000 mg/m2 cyclophosphamide and 800 mg/m2 thiotepa given over 4 days. Harvested marrow was purged with 100 micrograms/mL 4-hydroperoxycyclophosphamide, and all patients engrafted satisfactorily. The predominant side effects were myelosuppressive and gastrointestinal, and there were no deaths from toxic effects. Three of the 16 patients who showed a partial response after the outpatient phase of treatment achieved a complete response after high-dose therapy. The partial response seen in two more patients converted to a complete response at all sites except bone. The median time to disease progression for all patients in this study was 13 months, and the median survival was 22 months. Four of the original 30 patients remained without disease progression a median of 27 months from entry into the study. This study indicates that this dose-intense regimen can be safely administered, even with the use of purged marrow, with an acceptable toxicity profile. This approach results in a high response rate in women with metastatic breast cancer and could form the basis for a regimen to be tested in the high-risk adjuvant setting.

Sixteen-week dose-intense chemotherapy in the adjuvant treatment of breast cancer.

Fifty-three women with breast cancer were treated with a new 16-week dose-intense, chemotherapy regimen. Patients with operable breast cancer with 10 or more histologically positive axillary nodes were treated with this five-drug regimen that incorporated the concepts of weekly chemotherapy, sequential administration of antimetabolites, and continuous infusion of fluorouracil (5-FU). The chemotherapy regimen consisted of eight cycles (each of 2 wk duration) of 100 mg of cyclophosphamide/m2 orally on days 1-7, 40 mg of doxorubicin/m2 intravenous (IV) on day 1, 100 mg of methotrexate/m2 IV on day 1 with 10 mg of leucovorin rescue/m2 every 6 hours for six oral doses on day 2, 1 mg of vincristine IV on day 1, and 600 mg of 5-FU/m2 IV at hour 20 over 2 hours. A continuous infusion of 300 mg of 5-FU/m2 per day was given IV on days 8-9 of each 2-week cycle. The doses and schedule of drug administration were designed to minimize dosage reduction and treatment delay. At a median follow-up of 17 months, there have been eight relapses in the 53 patients. The actuarial 3-year disease-free survival is 80% (95% confidence interval, 62% to 90%). The major side effects were attributable to myelosuppression. Absolute neutrophil counts less than 250/microL were noted in 12 (23%) patients; seven patients (13%) required hospitalization for management of neutropenic fever. No treatment-related deaths occurred. Ninety-four percent of the planned doses were administered, and only 5% of the courses were delayed because of toxic reactions. The encouraging therapeutic data, manageable side effects, and our ability to deliver over 90% of the planned doses provide the rationale for a phase III comparison of this new dose-intense regimen and standard chemotherapy in patients with operable disease and positive axillary nodes.

CA-549: immunohistochemistry and serum levels in breast carcinoma and other neoplasms.

CA-549 is a high molecular weight acidic glycoprotein found in the serum of breast cancer patients. Detection of CA-549 in serum using an immunoradiometric assay has [1] correlated with disease course in breast cancer patients and [2] aided in establishing the diagnosis of breast cancer in patients with metastatic disease. This study examines the expression of CA-549 using immunohistochemistry in normal breast, benign breast disease, breast carcinoma, and a variety of other carcinomas. In addition, in 29 patients both serum and tissue samples were available for correlation. CA-549 was constitutively expressed in normal breast tissue, but immunohistochemical positivity was restricted either to the luminal aspect or entire cell membrane. All patients with benign breast disease had normal levels of CA-549 despite immunohistochemical positivity. Nearly all (98 percent) of breast carcinomas showed reactivity for CA-549, with a majority (82 percent) of the cases showing cytoplasmic positivity. In patients with both serum and tissue studied, those with cytoplasmic staining of the breast carcinomas had mean serum level of 174 U per ml (range 1.9 to 785), compared to 37.3 U per ml (range 2.1 to 86.8) in those with only membrane or luminal staining of tumor (p = 0.0578). Immunoreactive CA-549 was found in many normal epithelia and in other types of carcinomas. CA-549 is [1] constitutively expressed on the cell membrane of normal breast epithelium, [2] commonly present in the cytoplasm of breast carcinomas, and [3] found often in a variety of carcinomas.

Observations and proposed mechanism of N,N',N''-triethylenethiophosphoramide (thiotepa)-induced hyperpigmentation.

After receiving N,N',N''-triethylenethiophosphoramide (thiotepa) and cyclophosphamide intravenously, five women with metastatic adenocarcinoma of the breast developed a patterned hyperpigmentation confined to skin occluded by adhesive-containing materials. Determinations of thiotepa concentrations in occluded and nonoccluded skin, plasma, bandage with adhesive, and gauze containing sweat were performed. The results suggest that this alkylating agent is excreted onto the skin surface in sweat, accumulates beneath adhesive-containing bandages and electrocardiogram pads, and exerts a local toxic effect resulting in hyperpigmentation.

A new biomarker in monitoring breast cancer: CA 549.

Serum biomarkers are not very reliable in assessing outcome or predicting recurrence of breast cancer. Clinically, carcinoembryonic antigen (CEA) is widely used and is elevated in a majority of patients with metastatic breast cancer. However, it is falsely elevated in a wide range of nonmalignant conditions and correlates poorly with disease progression. We evaluated a newly described monoclonal antibody, CA 549, in an immunoradiometric assay which uses two monoclonal antibodies directed against tumor and milk fat globule membranes. CA 549 and CEA were studied in 682 patients, 331 of whom had breast diseases and 99 of whom were followed with multiple serum samples. Of 69 patients with benign breast diseases, 1.5% had elevated CA 549, 0% of 30 pregnant women had elevated CA 549, and 26% of patients with nonmalignant liver disease had CA 549 elevation. In metastatic cancer of prostate, ovary, endometrium, colon, and lung CA 549 was elevated in 12% to 50% of cases with levels less than 120 U/mL. In breast cancer, CA 549 was elevated in 11% of 88 patients who received adjuvant chemotherapy and had no evidence of metastasis; in 23% of 16 patients in complete remission after chemotherapy; in 63% of 52 patients in partial remission after therapy; and in 83% of 106 patients with progression of breast cancer compared with 63% with elevated CEA (P = .001). In diseases of the breast, CA 549 has a sensitivity In diseases of the breast, CA 549 has a sensitivity and specificity of 77% and 92% v 61% and 92% for CEA. Of 99 patients serially monitored with clinically documented breast cancer progression, regression, or stability of disease, CA 549 was statistically significantly superior to CEA in monitoring a greater than 25% change in those patients with metastatic progression (P = .03). CA 549 is a new serum marker that should be control tested in prospective clinical trials alone or in conjunction with other markers.