Weekly CODE chemotherapy with recombinant human granulocyte colony-stimulating factor for relapsed or refractory small cell lung cancer.

We used cisplatin, vincristine, doxorubicin, and etoposide (CODE) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) weekly for salvage chemotherapy in relapsed or refractory small cell lung cancer (SCLC). We reviewed the medical charts of patients between January 1993 and December 1996 at the National Nishi-Gunma Hospital. Twenty patients were treated with salvage chemotherapy. The overall response rate was 55.0%. The median survival time of extensive disease patients from the start of CODE therapy was 23 weeks and the 1-year survival rate was 21.0%. Toxicities were severe, especially in myelosuppression. CODE could be selected as a salvage therapy for chemotherapy- relapsed SCLC cases.

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.

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.

Risk factors for severe radiation pneumonitis in lung cancer.

BACKGROUND: Risk factors for severe radiation pneumonitis, which often spreads beyond treatment portals and may even be bilateral, have not been fully investigated. The purpose of this study was to identify important factors associated with severe radiation pneumonitis. METHODS: 111 cases of primary lung cancer, treated with radiotherapy or chemoradiotherapy, were retrospectively analyzed. RESULTS: Severe radiation pneumonitis occurred in 17 cases (15.3%). The ratio of interstitial change in lungs before radiotherapy and radiotherapy to the contralateral mediastinum with > 40 Gy in the radiation pneumonitis group (RP group) was significantly higher than in patients without radiation pneumonitis (control group) (47.1% vs 5.3%; P < 0.001 and 58.8% vs 27.7%; P = 0.037, respectively). Using logistic regression analysis, interstitial changes before radiotherapy and radiotherapy to the contralateral mediastinum of > 40 Gy were significant risk factors associated with severe radiation pneumonitis. CONCLUSIONS: These data suggest that pre-existing interstitial changes detected by chest radiography or computed tomography and radiotherapy to the contralateral mediastinum (> 40 Gy) may predict the development of severe radiation pneumonitis.

[Malignant hemangioendothelioma associated with chronic pyothorax].

A 67-year-old man was admitted to the hospital because of a fever. A chest CT scan showed multilobular heterogeneous shadows on the right side in the chest wall and the lung, but clinical examinations and examination of a biopsy specimen did not lead to a diagnosis. At autopsy, a hemorrhagic tumor was found on the right side in the chest wall. Microscopical examination showed that large atypical cells had proliferated and formed vascular structures, which were stained positively with anti-factor VIII antibody. The histological findings led to the diagnosis of malignant hemangioendothelioma. Chronic empyema-associated malignant hemangioendothelioma is rare.

[Removal of bronchial foreign bodies by suction with a bronchoscope].

We report two cases in which intrabronchial foreign bodies were removed with a fiberoptic bronchoscope. In both cases the foreign body was a seed of a small Japanese apricot. Atelectasis or obstructive pneumonia was seen on chest roentgenograms. The foreign bodies were associated with slight inflammation and polyps on the bronchial epithelium. The foreign bodies were removed by applying suction with a fiberoptic bronchoscope. This method may also be useful for removing other large, hard, uneven, and ball-like foreign bodies.

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.

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.

Phase I study of a carboplatin-cisplatin-etoposide combination chemotherapy in advanced non-small-cell lung cancer.

Cisplatin (CDDP)-containing chemotherapy has become the mainstay of clinical trials in unresectable non-small-cell lung cancer (NSCLC), but the role of chemotherapy in the routine management of NSCLC remains controversial. We conducted a phase I study with the combination carboplatin (CBDCA), CDDP, and etoposide (Etop) in unresectable NSCLC. CBDCA, at a starting dose of 80 mg/m2, on day 1, was combined with a fixed dose of CDDP (80 mg/m2, day 1) and Etop (80 mg/m2, days 1-3). Escalation was performed after four patients entered at each dose level. If no World Health Organization (WHO) grade 4 toxicity developed after the first cycle in more than half of the patients or WHO grade 3/4 toxicity in more than two thirds, the dose was escalated. The maximum tolerated dose was established at 300 mg/m2 for CBDCA. Thrombocytopenia and leukopenia were the dose-limiting toxicities. No grade 3/4 nonhematologic toxicities were seen. The recommended dose of CBDCA to be combined with CDDP (80 mg/m2, day 1) and Etop (80 mg/m2, days 1-3) is 280 mg/m2. This trial suggests that our combination chemotherapy may be effective in patients with advanced NSCLC. A multicenter phase II study based on these findings is now under way.

A phase II study of 72-hour continuous infusion consisting of cisplatin and 5-fluorouracil for treatment of non-small cell lung cancer.

A combination chemotherapy consisting of a 72-hour continuous infusion of cisplatin (CDDP; 100 mg/m2/72 h) and 5-fluorouracil (5-FU; 3 g/m2/72 h) was conducted for inoperable non-small cell lung cancer (NSCLC). Sixty patients were accepted for this study between June 1988 and December 1990. Forty-seven patients were male (median age 68). Thirty-four patients had stage III and 26 had stage IV disease. The response rate was 25.0% (95% confidence interval, CI, 14.0-36.0%), median survival was 15.7 months. In squamous cell carcinoma, the response rate was 35.5% (95% CI, 18.7-52.3%) and median survival was 15.1 months. In non-squamous cell carcinoma, the response rate was 13.8% (95% CI, 1.2-26.4%) and median survival was 17.7 months. There was a significant difference in response rate (p < 0.01), but no significant difference in survival (p = 0.36). Grade 3 leukopenia was 11.7%, grade 3 and 4 thrombocytopenia was 13.3%. Grade 3 nausea and vomiting were 8.3%. One patient had grade 4 renal toxicity. However, there was no treatment-related death. This regimen was well tolerated. In multivariate analysis, the significant parameters were CEA, performance status and response. In conclusion, 72-hour continuous infusion of CDDP and 5-FU for treatment of NSCLC provides similar response and toxicity as previously reported regimens using CDDP.

[Primary lung cancer in young patients].

We studied the clinical characteristics and prognosis of patients, 40 years old or younger, in whom primary lung cancer was diagnosed and treated at National Nishigunma Hospital between 1982 and 1993, and compared them with those of 978 patients more than 40 years old. Younger patients numbered 30 (3.0%). Females accounted for 16 of the 30 cases (53.3%), a proportion higher than the female: male ratio for the older patients (27.8%). There were more smokers among the older patients (72.8%) than among the younger patients (53.3%) (p < 0.01). Adenocarcinoma was significantly more common (19/30, 63.3% vs 43.8%, p < 0.05) and squamous cell carcinoma was less common (3.30, 10.0% vs 34.3%, p < 0.05) in the younger patients than in the older patients. Median survival time in younger patients was 30.0 months, and in older patients it was 14.6 months, but we found no significant difference in survival between younger and older patients. In the younger group, all the cases of stage I or II disease were discovered during mass screening.

[Clinical study of intrapleural administration of pirarubicin (THP-ADM) in the treatment of malignant pleural effusion secondary to lung cancer].

The efficacy of intrathoracic administration of pirarubicin (THP-ADM), a derivative of adriamycin, was evaluated in 20 patients with malignant effusion due to lung cancer. All 20 patients had no previous intrapleural therapy. According to the criteria of ECOG, eight patients were at performance status 1 (P.S.1), nine were P.S.2, and three were P.S.3. Fourteen patients were clinical stage IIIB, and six stage IV. The effusions were first completely drained by thoracocentesis or tube thoracostomy drainage, and 30 mg/m2 THP-ADM was instilled. Overall response rate was 50.0%. The response rate for treatment with tube thoracostomy drainage was 69.2%, which was significantly higher than that for treatment with thoracocentesis (14.3%). Significant difference in survival was not seen between the tube thoracostomy drainage group and the thoracocentesis group. There were no severe side effects. In conclusion, intrapleural administration of THP-ADM with tube thoracostomy drainage was considered to be useful for the control of malignant pleural effusion due to lung cancer.

[A case of long-term survival in a patient with small cell lung carcinoma with syndrome of inappropriate secretion of anti-diuretic hormone].

A 73-year-old man was admitted on April 1984 because of an abnormal shadow on chest X-ray. He was diagnosed as having small cell lung carcinoma (oat cell type) with inappropriate secretion of antidiuretic hormone (SIADH). Initial chemotherapy with cyclophosphamide, ACNU, vincristine, adriamycin, cis-platinum and etoposide was administered. The mass subsequently disappeared, and the serum sodium level normalized. About 2 years later, the patient developed a relapse of the primary lesion with hyponatremia. The same regimen as the initial chemotherapy was initiated and a complete response was again obtained. Similar episodes were repeated four times, and he died in April 1991. This patient survived for about seven years after the initial treatment without maintenance chemotherapy.

Equivalence relations in a class of distributed optical systems-lenslike media.

Equivalence properties of lenslike media with parabolic index profiles are analyzed on the basis of geometrical optics. By equivalent media we mean here those with the same ray-transfer matrix representation. An equivalence theorem is presented that provides a simple method of equivalent transformation of parabolic media. The practical importance of the equivalent transformation is that it leads to flexibility in the design of distributed optical structures, such as gas lenses and inhomogeneous optical fibers.