Takeyuki Makimoto

Serum Pro-Gastrin-Releasing Peptide Is a Useful Marker for Treatment Monitoring and Survival in Small-Cell Lung Cancer

We investigated the usefulness of serum pro-gastrin-releasing peptide (Pro-GRP) as a tumor marker for diagnosis, treatment monitoring and the prediction of relapse and prognosis in patients with small-cell lung cancer (SCLC). Serum samples were obtained from 127 patients with primary lung cancer (48 patients with small-cell carcinoma, 31 with adenocarcinoma, 36 with squamous cell carcinoma and 11 with large-cell carcinoma). The cutoff levels of serum Pro-GRP and neuron-specific enolase (NSE) were set at 46 pg/ml and 10 ng/ml, respectively. The specificity of Pro-GRP was significantly higher than that of NSE (Pro-GRP: 93.7%, NSE: 65.8%, p < 0.01). According to the histological type of lung cancer, the positive rates of Pro-GRP were 75% (36/48) in the small-cell carcinomas, 9.7% (3/31) in the adenocarcinomas, 5.6% (2/36) in the squamous cell carcinomas and 0% (0/10) in the large cell carcinomas. The median levels of Pro-GRP in limited disease (LD) and extensive disease (ED) patients were 199 and 295.5 pg/ml, whereas those of NSE were 14.8 and 29.3 ng/ml, respectively. The positive rates of Pro-GRP in LD and ED patients were 80.0% (16/20) and 71.4% (20/28), whereas those of NSE were 70.0% (14/20) and 89.3% (25/28), respectively. The positive rate of NSE tended to elevate with the progression of disease, whereas that of Pro-GRP was already high at an early stage. Among the 29 patients with SCLC who could be followed, the serum Pro-GRP levels of 18 responders were significantly decreased after treatment (p < 0.01), whereas those of the 11 nonresponders were not significantly different between before and after treatment (p = 0.72). In the 9 patients with SCLC who relapsed, the serum Pro-GRP levels were again elevated at the time of relapse. Seventeen patients whose ratio of the Pro-GRP level after treatment to the level before treatment was below 50% (taking the levels before treatment as 100%) survived significantly longer than did the patients whose ratio was over 50% (p < 0.01). The results of the present study suggest that serum Pro-GRP has high specificity and could be a useful marker of SCLC for treatment monitoring and prognosis.

CYFRA 21 -1: An Indicator of Survival and Therapeutic Effect in Lung Cancer

CYFRA 21-1 is a new tumor marker using two different monoclonal antibodies which recognize the divergent epitope on the N- or C-terminal region of domain 2 of cytokeratin 19 fragment, respectively. In this study, we investigated the relationship between levels of CYFRA 21-1 and survival duration, as well as the efficacy of chemotherapy associated with changes in CYFRA 21-1. Serum samples were obtained from 87 patients with nonoperable lung cancer (35 cases with squamous-cell carcinoma, 33 with adenocarcinoma, 3 with large-cell carcinoma, and 16 with small-cell carcinoma). The cutoff point was set at 3.5 ng/ml. In a CYFRA 21-1 assay, significantly more patients with squamous-cell carcinoma and adenocarcinoma were positive compared to patients with small-cell and large-cell carcinomas (p = 0.0017). Following chemotherapy, blood levels of CYFRA 21-1 decreased significantly in responders versus nonresponders (p = 0.0246). A significant correlation was noted between survival periods and pretreatment levels of CYFRA 21-1 (p = 0.0036). The present study suggests that CYFRA 21-1 might be useful as a possible indicator of survival and therapeutic effect for lung cancer.

A phase II study of combined chemoradiotherapy for limited disease-small-cell lung cancer.

A study to evaluate the efficacy of cisplatin, doxorubicin, and etoposide chemotherapy with combined radiotherapy was undertaken in 26 patients with limited disease-small-cell lung cancer. Patients were treated with cisplatin (80 mg/m2) intravenously (i.v.) on day 1, doxorubicin (30 mg/m2) i.v. on day 1, and etoposide (80 mg/m2) i.v. on days 1, 3, and 5, every 4 weeks for four cycles. Thoracic irradiation of 40 Gy in 20 fractions was delivered during 4 weeks to the primary site starting on day 8 of the second cycle of chemotherapy. The objective response rate was 100%. A complete response was observed in 10 patients (38%). The median survival time was 23 months, and the 3-year survival rate was 42%. Seven patients (27%) continued to survive at least 8 years and remain free from disease. Grade III/IV leukopenia was observed in 25 patients (96%). Grade III/IV thrombocytopenia developed in 19 patients (73%). Grade III/IV esophagitis was not seen. Interstitial pneumonitis occurred in two patients. This regimen is effective and has acceptable toxicity for use in the treatment of limited disease-small-cell lung cancer.

A phase II study of carboplatin-cisplatin-etoposide combination chemotherapy in advanced non-small-cell lung cancer

It is reported that the combination of cisplatin (CDDP) and carboplatin (CBDCA) is synergistic in vitro. The objective of this study was to evaluate the therapeutic effect and safety of the two platinum compounds in combination with etoposide in the treatment of non-small-cell lung cancer (NSLC). Forty patients were registered. Based on the results of a phase I study, patients were treated with CDDP (80 mg/m2 i.v. on day 1), CBDCA (280 mg/m2 i.v. on day 1), and etoposide (80 mg/m2 i.v. on days 1-3). Of the 40 patients, 30 were men and 10 women. Histology revealed adenocarcinoma(AC) (n = 20), squamous cell carcinoma(SCC) (n = 18), and large cell carcinoma(LCC) (n = 2). Staging: IIIA (n = 3); IIIB (n = 17); and IV (n = 20). A 32.5% overall response rate [13 of 40; 95% confidence interval (CI) 18-47%] was achieved. The response rates in patients with SCC and AC were 55.6 and 10.0% (p < 0.005), respectively. The median duration of response was 47.1 weeks and the overall median survival time was 57.1 weeks. Leukopenia and thrombocytopenia--World Health Organization (WHO) grade IV--occurred in nine and 11 patients, respectively. Nonhematological toxicities were mainly nausea, vomiting, and alopecia. In conclusion, further investigations of this regimen are warranted in the treatment of NSLC.