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Background: Lactoferrin is an iron-binding glycoprotein first identified in breast milk as a protein product of mammary epithelial cells. Its immunomodulatory functions include activation of NK and lymphokine-activated killer cells and enhancement of PMN and macrophage cytotoxicity. Studies in animal models have shown promising anti-cancer activity. The purpose of the present study was to evaluate the safety and tolerability of talactoferrin alfa (talactoferrin; TLF) in humans, as well as pharmacokinetics and pharmacodynamics., Methods: Ten adult patients with progressive advanced solid tumors who had failed conventional chemotherapy were administered oral TLF at doses from 1.5 to 9 g/day, using a 2 weeks on, 2 weeks off schedule. Patients were evaluated for drug toxicity, tumor growth rate, talactoferrin pharmacokinetics and cytokine markers., Results: Talactoferrin was very well tolerated. No hematological, hepatic, or renal toxicities were reported. A single patient had Grade 2 diarrhea, and there were no Grade 3 or 4 toxicities. Following oral administration, significant levels of talactoferrin were undetectable in circulation, but a statistically significant increase in circulating IL-18, a pharmacodynamic indicator of talactoferrin activity, was observed. Of the eight patients who were radiologically evaluable, five (63%) had stable disease by RECIST criteria two months after start of therapy, including one patient with a minor response. Seven patients (88%) had a decrease in their tumor growth rate. The three patients with non-small cell lung cancer (NSCLC) all survived for at least one year following the start of talactoferrin monotherapy., Conclusions: Talactoferrin is a promising, well-tolerated new agent that should be evaluated further in patients with refractory metastatic cancer.

Forty-six patients with metastatic non-small-cell lung cancer (NSCLC) were treated with a combination of high-dose cisplatin, etoposide, and mitomycin. Thirty-four patients (74%) had a performance status of 1, and 39 patients (85%) had adenocarcinoma. Of the 42 patients evaluable for response and toxicity, four achieved a partial response (10%); no patient achieved a complete response. Seven patients who had received prior chemotherapy showed no major response. The median survival of all 42 patients was 23 weeks. Myelosuppression was the major dose-limiting toxicity for this regimen, and 12 of 46 patients (26%) developed neutropenic fever requiring hospitalization and parenteral antibiotics. Of the 12 patients with severe neutropenic fever, one patient died because of toxicity. Nonhematologic toxicities, including azotemia, peripheral neuropathy, nausea, vomiting, and hearing loss were transient and modest. We conclude that high-dose cisplatin combined with etoposide and mitomycin is a relatively toxic regimen with a low response rate. Further evaluation of the combination as given in this trial is not warranted.

Eighteen patients with advanced solid tumors were treated in a phase I study of cisplatinum in combination with recombinant alpha-2a interferon (Roferon-A, Hoffman-LaRoche, Inc, Nutley, NJ). Roferon-A was administered at a dose of 5 MU/m2 S.C. three times a week and the dose levels of cisplatinum were 15, 20, 25, 33, and 42 mg/m2/week given intravenously. All patients experienced grade I/II fatigue, nausea and vomiting. Grade III toxicity occurred in 4/6 patients at dose level 4. The dose limiting toxicities were myelosuppression [leukopenia (two patients), neutropenia (one patient), thrombocytopenia (one patient)], vomiting (one patient) and severe fatigue leading to a decrease in performance status (one patient). One patient with non-small cell lung carcinoma had a mixed response and another a minor response. The recommended dose level of this combination for phase II studies is cisplatinum 25 mg/m2/week and Roferon-A 5 MU/m2 three times a week.

Long duration of responses to chemotherapy in patients with malignant pleural mesothelioma (MPM) is rare. The authors report a patient with inoperable MPM who achieved complete remission with combination chemotherapy of cyclophosphamide, doxorubicin, and cisplatin. 5-fluorouracil and mitomycin C (FM) induced another remission after recurrence of the tumor. Retreatment with FM after chemotherapy had been stopped for 20 months yielded another continuing response. The overall tumor-control time is more than 4 years. Literature reviews and the authors' results suggest that MPM may be a chemosensitive tumor in some patients. Additional evaluations of CAP, FM, and methotrexate combination regimens in this disease should be considered.

Fourteen patients with extensive disease small cell bronchogenic carcinoma (SCBC) received ifosfamide at 2,000 mg/m2/day for 5 consecutive days with simultaneous mesna and vincristine while 26 patients with extensive disease non-small-cell bronchogenic carcinoma (N-SCBC) received the same regimen without vincristine. Eight partial responses (57%) were observed with a 40-week median survival in the case of SCBC and four partial remissions (15%) with a 31-week median survival in N-SCBC. Granulocytopenia was the dose-limiting toxicity, whereas urotoxicity was well controlled with mesna. Neuropsychiatric toxicity consisted of anxiety, agitation, confusion, and hallucination. Neurobehavioral testing detected worsened performance during ifosfamide treatment. Ifosfamide is one of the few active agents in N-SCBC.

Twenty-six patients with a limited-disease presentation of small-cell bronchogenic carcinoma (SCBC) had surgery after achieving a partial remission with three cycles of chemotherapy. Persistent SCBC was found in 15 patients (58%), non-small-cell bronchogenic carcinoma (NSCBC) in six patients (23%), and no malignancy in five patients (19%). Twelve patients have died since surgery. Tumor-node-metastasis (TNM) staging prior to or after chemotherapy was not predictive of outcome, but an N0 status found at pathological examination of the surgical specimen was predictive of long-term survival. Median survival for this group of patients was 25 months. Adjuvant surgery is feasible and may be beneficial.

The pharmacology, toxicity, and therapeutic effectiveness of etoposide (VP-16) given by the intrapleural route were examined in a phase I trial. Ten patients with malignant pleural effusion received 100, 150, or 225 mg/m2 VP-16 infused over 2 h into the pleural space after drainage of pleural fluid. The administration of VP-16 was tolerated well, with no local pain, increase in cough, dyspnea, or infection. Myelosuppression was mild at doses of 150 mg/m2 or less but severe at 225 mg/m2. Drug levels were followed in both plasma and pleural fluid for up to 12 h. Clearance of VP-16 from the pleural cavity was low at 2 ml/min m2. Peak pleural-fluid drug levels in patients receiving 225 mg/m2 exceeded 300 micrograms/ml, whereas peak drug concentrations in corresponding plasma samples obtained at the same time amounted to less than 10 micrograms/ml. Serial chest X-rays showed no disappearance of pleural effusion in nine evaluable patients. However, follow-up investigation of pleural fluid characteristics [carcinoembryonic antigen (CEA), lactic dehydrogenase (LDH), and cytologic examination] suggested some evidence of local therapeutic benefit.

One hundred sixty-seven evaluable patients with non-small-cell lung cancer were randomized to receive high-dose cisplatin and vindesine (PVD), or cisplatin and VP-16-213 (etoposide epipodophyllotoxin) (PVP), or cisplatin with VP-16-213 and vindesine (PVPVD). The patient distribution and characteristics were similar in all the treatment arms. The response rate differences (35% in PVD arm, 30% in PVP arm, and 22% in PVPVD arm) were not statistically significant (P = .33). Response durations were 43 weeks in the PVD arm, 20 weeks in the PVP arm, and 27 weeks in the PVPVD arm. Median survival was 29 weeks in the PVD and PVP arms and 28 weeks in the PVPVD arm. Median survival time of responding patients was 76 weeks in the PVD arm and 65 weeks in the PVP arm; 78% of patients were alive at 22+ to 87+ weeks follow-up in the PVPVD arm. Myelosuppression was similar in all three treatment arms. Significantly more azotemia occurred in the PVD arm than in the PVP and PVPVD arms (P = .002), and significantly more neuropathy in the PVD and PVPVD arms than in the PVP arm (P = .003 and .005). All the treatment arms have similar antitumor activity in non-small-cell lung cancer, but the PVP combination is slightly less toxic than the PVD and PVPVD treatment arms.

Risk factors for brain metastasis in small cell lung cancer were studied in 260 patients without brain metastasis at presentation who were treated on 5 protocols. The first three protocols offered elective brain irradiation (EBI) to all available patients after 2 or 3 courses of chemotherapy (early EBI), whereas the other two offered it after 5 or 6 courses of chemotherapy (late EBI). The overall incidence of brain metastasis was higher in the late EBI group than in the early EBI group (23.6% vs. 14.3%, p = 0.08), primarily due to higher incidence of brain metastasis developing before EBI in the former. There was a higher incidence of brain metastasis in patients without than in patients with bone marrow metastasis (21.4% vs. 6.8%, p = 0.04), in patients less than 60 years old than in patients 60 years or older (23.4% vs. 13.4%, p = 0.06), and in patients with than in patients without bone metastasis (30.2% vs. 16.8%, p = 0.07). Major risk factors for short brain metastasis-free survival were bone metastasis (p = 0.008), late EBI (p = 0.03), and failure to achieve complete remission after induction chemotherapy (p = 0.001) or as a best response (p = 0.0001). The early EBI group had a longer brain metastasis-free survival than the late EBI group, even among patients with bone metastasis (p = 0.02) or bone marrow metastasis (p = 0.05) and those who achieved complete remission after induction chemotherapy (p = 0.06) or as a best response (p = 0.05). These results indicate that timing of EBI is a critical factor in brain metastasis in patients with small cell lung cancer. There was no difference in overall survival between the two groups, however, even among patients who achieved complete remission as a best response.

A phase II clinical study of dihydroxyanthracenedione ( DHAD ) was conducted in 50 patients with advanced lung cancers. DHAD was administered intravenously on a 5-day schedule repeated every 4 weeks. Most patients had adenocarcinoma (46%), and had received previous chemotherapy (66%) and radiation therapy (50%). Among 41 evaluable patients, there were four partial remissions, eight disease stabilizations and 29 disease progressions. Remissions were more common among previously untreated patients (20% vs. 4%), particularly in patients with adenocarcinoma and large cell carcinomas of whom 3/10 (30%) responded. Responses lasted 9+, 9, 7, and 3 months, respectively. Cardiac toxicity was not observed. Other toxicities were tolerable. DHAD is a potentially useful agent for the therapy of adenocarcinoma and large cell lung cancers.

Esophageal complications from combined chemoradiotherapy (CCRT) were analyzed in 55 patients with limited non-small cell lung cancer. CCRT consisted of chemotherapy (cyclophosphamide, doxorubicin (Adriamycin), and cisplatin: CAP) and chest irradiation (5000 rad in 25 fractions/5 weeks). Forty-five patients received two courses of CAP, followed by five weekly courses of low dose CAP and irradiation followed by maintenance courses of CAP (Group 1). Ten patients received concomitant CCRT from the onset of treatment (Group 2). Esophagitis occurred in 80% of all patients. Severe esophagitis occurred in 27% of patients of Group 1 and 40% of patients of Group 2. Esophageal stricture or fistula developed in 1 of 45 (2%) patients in Group 1, and 3 of 10 (30%) patients in Group 2 (p less than 0.025). Weekly low-dose chemotherapy administered concomitantly with chest irradiation (R) at the onset of treatment significantly increases esophageal complications. A review of the literature suggests that CCRT may be used safely with split courses of R. The duration between onset of chemotherapy either before or after R should be greater than one week.

We have studied the clinical impact of elective brain irradiation (EBI) in patients with locally advanced, non-small cell lung cancer (LA-NSC). All patients received combination chemotherapy (cyclophosphamide + doxorubicin (Adriamycin) + cisplatin = CAP) or CAP plus radiotherapy as the initial treatment for their active tumor or as an adjuvant therapy. Of 97 evaluable patients, 46 were randomized to receive EBI (3 000 rad in 10 fractions given over two weeks). The characteristics of both groups were comparable by sex, age, performance status, pretherapy weight loss, histologic cell type, clinical staging, and type of prior therapy. EBI significantly decreased the incidence of central nervous system (CNS) metastasis in the treated group compared to the control group (4% vs 27%, p = .002). CNS involvement occurred in the treated group after failure at other sites whereas 12 of 14 control patients had CNS metastases as the first site of relapse. EBI decreased the incidence of CNS metastasis in all prognostic categories. Using multivariate analysis, the beneficial effect was shown to be significant in females, patients with good performance status, weight loss less than 6%, squamous cell histology, state III disease or no prior therapy. EBI significantly increased CNS metastasis-free interval with a beneficial effect that was significant in males, patients with weight loss less than 6%, squamous cell histology or responders. Although no survival benefit was observed for the treated group because of the adverse effect from other relapses, EBI will become more important as better treatment programs are developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Fourteen patients with untreated small cell bronchogenic carcinoma were treated initially with 2 chemotherapy courses of cyclophosphamide (1.5 g/m2 days 1-3), 4-dimethyl epipodophylloxtin (200 mg/m2 days 1-3), vincristine (1.5 mg/m2 days 1 and 3), and with Adriamycin (80 mg/m2 day 1) in 8 patients and without Adriamycin in 6 patients. To modify hematopoietic toxicity from these high doses of chemotherapy, autologous marrow collected and frozen before storage was thawed and infused after each of these high-dose therapies. After this therapy patients received prophylactic brain irradiation (3000 rad), 4 courses of usual doses of these same drugs and then 5000 rad chest irradiation if there was still evidence of disease (PR) or randomized to radiation if in complete remission (CR). Response rate was high, with 54% CR and 46% PR, a total of 100%. However, a median response duration of 41 weeks and median survival of 56 weeks, are similar to other chemotherapy programs. Toxicity was mild except for cardiac arrhythmias when Adriamycin was included. The reasons for no therapeutic increment are discussed.

We have described a patient with small cell cancer of the lung manifested as the Eaton-Lambert syndrome. Primary therapy proved effective in reversing the syndrome, whereas anticholinesterase agents did not. This case illustrates the value of primary therapy for the tumor-produced syndrome and the need to avoid losing time with symptomatic therapy.

The effect of brain irradiation on myelosuppression was studied in patients with untreated small-cell lung cancer (SCLC) by comparing 24 patients who received brain irradiation for brain metastasis at presentation (irradiated patients) with 24 control patients who were selected by matching ages and non-CNS metastatic sites with those of irradiated patients. All patients were evaluated during the first three courses of chemotherapy. More irradiated patients than control patients had chemotherapy dose reductions from the starting dose level for the second (nine of 22 v two of 24; P = .03) and the third (nine of 18 v three of 20; P = .05) courses of chemotherapy. Overall, more irradiated patients had chemotherapy dose reductions than did control patients (11 of 22 v three of 24; P = .01). The difference was highly significant even after other variables were considered in a multivariate analysis (P less than .001). Myelosuppression was more severe in irradiated patients for WBCs (P = .01) and for platelets (P = .05). When the second course of chemotherapy was administered at the same dose levels as in the first course, irradiated patients had greater decreases in nadir counts after the second course compared with the first course than did control patients. Irradiated patients had a higher incidence of infectious complications than did control patients (14 of 24 v six of 24; P = .02), particularly after the second course of chemotherapy (seven of 22 v one of 24; P = .04). There were four treatment-related deaths due to sepsis in irradiated patients. Following brain irradiation given concurrently with intensive chemotherapy, close monitoring of myelosuppression and adjustments of chemotherapy doses are advised.

Forty-one patients with unselected advanced non-small cell lung cancer were treated with a combination of etoposide and cisplatin. A response rate of 19%, a 78-week median survival of responders, and a 36-week overall median survival were observed.

Fourteen evaluable patients with small cell bronchogenic carcinoma received tiazofurin, an inhibitor of inosine monophosphate dehydrogenase, that progressed after one combination chemotherapy. No objective remission was observed at the dosage of 800 mg/m2 for 5 consecutive days. Toxicity was moderate.

The efficacy and toxicity of high-dose chemotherapy with autologous bone marrow transplantation (ABMT) was studied in 32 patients with untreated limited small-cell bronchogenic carcinoma (SCBC). Ten patients received three courses of induction therapy consisting of vincristine (VCR) (1.5 mg X 2), ifosfamide (5 g/m2), and Adriamycin (Ad; Adria Laboratories, Columbus, Ohio) (60 mg/m2). Patients then received two courses of intensification therapy with cyclophosphamide (CYT) (4.5 g/m2), 4' demethyl-epipodophyllotoxin-d-D-ethylidene glucoside (VP-16-213) (600 mg/m2) and VCR (2 mg) with ABMT. Another 22 patients received induction therapy with VCR, CYT (600 mg/m2), Ad (50 mg/m2), and VP-16-213 (180 mg/m2). All 22 patients also received intensification therapy of the same dose of CYT (4.5 g/m2) and VP-16-213 (600 mg/m2). Nine patients also received high-dose methotrexate (MTX), four patients received Ad (40 to 60 mg/m2), and two patients received both Ad and MTX. After intensification, patients received elective prophylactic brain irradiation (3,000 rad) and chest irradiation (5,000 rad). After induction therapy, there were 13 (41%) complete remissions (CR) and 17 (53%) partial remissions (PR). After intensification therapy, there were 22 CRs (69%) and 10 PRs (31%). Median survival for all patients was 14 months (range, 5 to 59+). Of the 13 patients who received intensification therapy in CR, five remain disease free (DF), four for 4 years or longer. Of the nine patients to achieve CR with intensification, only one is DF. No patient died during intensification. In conclusion, intensification with high-dose chemotherapy can increase the CR rate, and this approach is most likely to show long-term benefits in patients with minimal disease (CR) at the beginning of intensification therapy.

A prospective randomized study was done to determine the effect of different doxorubicin (Adriamycin [ADR], Adria Laboratories, Columbus, OH) administration (schedules every week versus every 3 weeks) on the productivity of a cyclophosphamide, ADR, cisplatin (CAP) chemotherapy regimen for patients with non-small cell lung cancer (NSCLC). Electrocardiograms, multigated cardiac scans, echocardiograms, and endomyocardial biopsies were done serially for cardiac monitoring. Of 102 patients, 47 ahd inoperable limited disease (LD), 47 had extensive disease (ED), and eight had no evidence of disease. In the last group chemotherapy was given adjuvantly. Fifty-one patients were entered into each treatment arm. The groups were formed according to extent of disease and were comparable in terms of patient characteristics. In these groups, the overall response rates using both schedules in LD patients were similar: in patients without chest irradiation previously, there was a response of 35% with ADR weekly, and 31% with ADR triweekly; in LD patients with chest irradiation previously, the response was 20% with ADR weekly, and 25% with ADR triweekly; and in ED patients, 16% with ADR weekly, and 11% with ADR triweekly. There was no significant difference in survival between the two treatment groups. However, results for all responders suggested a longer duration of response with weekly than with triweekly ADR (complete plus partial response: 35.8 versus 11.4 weeks, P = 0.06; minor response: 34 versus 11.5 weeks, P = 0.003, respectively). Results also suggested that weekly ADR was less cardiotoxic than triweekly ADR: 29% of patients in the former group had no changes or only minor changes in endomyocardial biopsy results, whereas all patients in the latter group had at least grade 0.5 changes at a similar dosage. The median doses of weekly ADR were higher at the same endomyocardial biopsy-defined toxicity levels. No correlation was found between toxic effects defined by endomyocardial biopsy results and those defined by noninvasive monitoring techniques, although the number of patients assessed was small. Weekly ADR produced less granulocytopenia and a lower incidence of fever (6% versus 16%, P less than 0.001) than did triweekly ADR. Alopecia, nausea, vomiting, and diarrhea were significantly less for weekly ADR than triweekly Adr (P less than 0.0005, less than 0.0005, and less than 0.005, respectively). These data suggest that weekly ADR can achieve the same therapeutic results as the standard triweekly regimen with less cardiotoxicity, myelotoxicity, alopecia, diarrhea, nausea, and vomiting in patients with NSCLC.

A pilot study was conducted using a combination of cisplatin (70 mg/m2 i.v., day 1), etoposide (60 mg/m2 i.v., days 1 through 5), continuous-infusion 5-fluorouracil (800 mg/m2 i.v., days 1 through 5), and allopurinol (600 mg p.o., days 1 through 7). Treatment was repeated every 3-4 weeks. Ten patients with metastatic non-small cell lung cancer were treated. Significant toxicities were observed, including electrocardiographic changes simulating acute myocardial infarction in three patients. There was no objective response, therefore the study was closed early according to its design.

Thirty-six patients with lung cancer, 24 with prior chemotherapy and 12 without prior chemotherapy, received iv melphalan at doses ranging from 20 to 40 mg/m2 of body surface area. Patients who showed moderate myelosuppression and remained in the study were also investigated to determine if cyclophosphamide (300 mg/m2) administered 1 week before the identical dose of i.v. melphalan modified the hematopoietic toxicity of melphalan (cyclophosphamide priming). In this study, the activity of melphalan was minimal, four minor responses with no partial or complete responses. Three of these minor responses were in previously untreated patients. The major toxicity was hematopoietic and the maximum tolerated i.v. dose was 20 mg/m2 in the patients previously treated with chemotherapy and 30 mg/m2 in those without prior chemotherapy. Cyclophosphamide priming did not reduce the myeloid toxicity. Myelosuppression was more severe in the course that included cyclophosphamide. Recovery, however, appeared to be similar in both courses. I.v. melphalan at these doses has minimal activity in lung cancer. Cyclophosphamide administered 1 week before i.v. melphalan does not decrease the myelosuppression but should be investigated further for its effect on the rate of wbc and neutrophil count recovery.

Forty-three patients with limited-disease, inoperable non-small cell lung cancer received two intravenous courses of cyclophosphamide, Adriamycin, and cisplatin (CAP) chemotherapy over a 6-week period. This was followed by 5 weeks of combined chemoradiotherapy (CCRT) consisting of low weekly doses of CAP for 5 weeks plus 50 Gy continuous X ray therapy (XRT) to the primary tumor site. Chemotherapy was continued until disease progression occurred or until the total dose of Adriamycin reached 450 mg/m2, whichever came first. CCRT improved the response rate [complete response (CR) plus partial responses (PR)] from 25% after two courses of CAP alone to 65% after CCRT. Previous response to two courses of CAP influences response subsequent to CAP plus XRT. A pretherapy weight loss of 6% or greater had a significant adverse effect on both response and survival time. The median survival time for all patients was 50 weeks; patients whose disease responded to treatment survived significantly longer than patients with nonresponding disease. The median time until disease progression was 37 weeks. Twenty-seven patients relapsed. The first sites of relapse were local in 30% of the patients, distant in 56% of them, and both local and distant in 15%. Severe esophagitis occurred in 30% of the patients and was dose-limiting. The administration of CCRT resulted in an improved response rate compared with the rates reported in previous studies of chemotherapy or radiotherapy alone. Further improvement of the CCRT program is needed to increase long-term survival time and to decrease esophageal toxicity.

Fourteen patients with brain metastases from previously untreated small-cell lung cancer (SCLC) were treated with three courses of systemic chemotherapy as an initial mode of treatment. Whole brain irradiation was given concurrently with the fourth course of chemotherapy. The chemotherapy consisted of cyclophosphamide, 600 mg/m2 intravenously (IV) on day 1; doxorubicin, 50 mg/m2 IV on day 1; vincristine, 1.5 mg IV days 1 and 5; and etoposide, 60 mg/m2 IV days 3 through 5; all repeated every 3 weeks with dosage adjustments. There were ten men and four women, with a median age of 59 years (range, 47 to 75). Six patients had multiple brain lesions, and the brain was the sole site of distant metastasis in four patients. Three patients were inevaluable for response in the brain, as two died early and the third dropped out of the trial too soon. Brain lesions responded to chemotherapy in nine (one complete remission [CR], eight partial remissions [PR]) of 11 (82%) evaluable patients, and objective responses in the extracranial lesions were documented in nine (one CR, eight PR) of 12 (75%) evaluable patients. Median survival was 34 weeks (range, 1 to 93), and two patients are still alive. Toxicity was significant, with severe granulocytopenia (less than 500/microL) and thrombocytopenia (less than 50,000/microL) observed in 85% and 15% of patients, respectively. Six patients had major infectious complications, which resulted in septic deaths in two. However, there was no deterioration of neurologic status during the initial phase of treatment with chemotherapy. We conclude that systemic chemotherapy alone can induce objective regression of metastatic brain lesions in patients with previously untreated SCLC.

Carcinoembryonic antigen (CEA) was measured in 147 patients at diagnosis of small cell lung cancer; 17% of patients with limited disease and 51% with extensive disease had an abnormal CEA level (greater than 10 ng/ml). The median level was higher in extensive than in limited disease (11 ng/ml and 5.8 ng/ml, respectively; P less than 0.001). Multivariate analysis showed CEA level greater than or equal to 50 ng/ml to be an adverse prognostic factor (P = 0.02); median survival at this level was shorter than at less than 50 ng/ml (7 and 46 weeks, respectively; P = 0.002). No consistent directional changes of follow-up CEA values were observed in patients with initially normal CEA levels, but normalization of levels occurred in complete responders. We recommend that CEA be measured in this disease at diagnosis as an additional prognostic factor and that patients with abnormal initial CEA levels have follow-up measurements to aid in evaluating response.