Use of carcinoembryonic antigen in small cell lung cancer. Prognostic value and relation to the clinical course 1.

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.

I.v. melphalan in carcinoma of the lung: effect of cyclophosphamide priming on hematopoietic toxicity.

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.

High-dose intensification therapy with autologous bone marrow support for limited small-cell bronchogenic carcinoma.

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.

Esophageal complications from combined chemoradiotherapy (cyclophosphamide + Adriamycin + cisplatin + XRT) in the treatment of non-small cell lung cancer.

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.

Primary therapy for small cell lung cancer reversing the Eaton-Lambert syndrome.

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.

Randomized trial of three combinations of cisplatin with vindesine and/or VP-16-213 in the treatment of advanced non-small-cell lung cancer.

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.

Systemic combination chemotherapy as primary treatment of brain metastasis from lung cancer.

Five patients with primary lung cancer metastatic to the brain were treated with systemic combination therapy alone. One patient had had unsuccessful radiation therapy, while the other four received chemotherapy as the primary modality of treatment. Response was observed in all five patients. The concept of the blood-brain barrier and the role of systemic chemotherapy in metastatic cancer to the brain are discussed.

Chemotherapy for advanced adenocarcinoma and squamous cell carcinoma of the lung with etoposide and cisplatin.

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.

Role of elective brain irradiation during combined chemoradiotherapy for limited disease non-small cell lung cancer.

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)

High-dose chemotherapy and autologous bone marrow transplantation for the treatment of small cell lung carcinoma.

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.

Computed tomography and routine chest radiography in oat cell carcinoma of the lung.

Computed tomography (CT) scans of the chest and routine postero-anterior and lateral chest films were compared in 32 patients with pathologically proven oat cell carcinoma of the lung. Nineteen of the 32 patients were examined prior to any form of therapy. Overall, CT gave more information about the extent of disease. The significance of this information may be of little value because the routine chest films also demonstrated mediastinal involvement, although to a lesser degree. Computed tomography of the chest should not be the initial diagnostic staging procedure in oat cell carcinoma, but used selectively. It can be quite useful in patients who have a partially opacified lung, possibly for the evaluation of mediastinum after therapy, and for the evaluation of possible abdominal metastases.