Combination chemotherapy for advanced lung cancer.

Lung cancer is now a major public health problem in Thailand. This study was undertaken to gain some preliminary data regarding the potential effectiveness in treating advanced non-small cell lung carcinoma (NSCLC) using an ifosfamide combination therapy IA(E)P. A clinical study was made of all 50 patients (Thais) with histologically proven, advanced NSCLC admitted to the University of Siriraj Hospital between 1985 and 1987 and followed up until February 1992. Survival was calculated for responders and non-responders as distinct groups, and for the different histological tumors among the responders. There were 22 cases of adenocarcinoma, 13 large cell carcinoma, and 15 squamous carcinoma. Twenty-seven out of 50 (54%) responded to treatment. The median survival of the response group was 17 months, compared with 5.5 months in the nonresponse group. The longest survival period was seen in patients with large cell carcinoma. The results suggest that moderate success might be expected in selected patients using the IA(E)P. Further work should be undertaken in developing countries using controlled clinical trials to more fully determine the efficacy of IA(E)P in treating NSCLC.

Exposure to N-nitroso compounds in a population of high liver cancer regions in Thailand: volatile nitrosamine (VNA) levels in Thai food.

The recent case-control studies in Thailand indicate that a high incidence of liver cancer in Thailand has not been associated with common risk factors such as hepatitis B infection, aflatoxin intake and alcohol consumption. While the infestation by the liver fluke Opisthorchis viverrini (OV) accounted for the high risk in north-east Thailand, there was no such exposure in the other regions of the country where the incidence of liver cancer is also high. Case-control studies suggest that exposure to exogenous and possibly endogenous nitrosamines in food or tobacco in betel nut and cigarettes may play a role in the development of hepatocellular carcinoma (HCC), while OV infestation and chemical interaction of nitrosamines may also be aetiological factors in the development of cholangiocarcinoma (CCA). Over 1800 samples of fresh and preserved food were systematically collected and tested between 1988 and 1996. All the food items identified by anthropological studies to be consumed frequently in four major regions of Thailand were analysed for volatile nitrosamines using gas chromatography combined with a thermal energy analyser. Relatively high levels of N-nitrosodimethylamine (NDMA), N-nitrosopiperidine (NPIP) and N-nitrosopyrrolidine (NPYR) were detected in fermented fish ("Plasalid"). NDMA was also detected at levels ranging from trace amounts to 66.5 microg/kg in several salted and dried fish ("Larb-pla" and "Pla-siu"). NDMA and NPYR were frequently detected in several vegetables, particularly fermented beans ("Tau-chiau") at levels ranging between 1 and 95.1 microg/kg and 0-146 microg/kg, respectively. The possible role of nitrosamines in Thai food in the aetiology of liver cancer (HCC, CCA) is discussed.

Microsatellite alterations in non-small cell lung cancer.

Genetic alterations at 12 dinucleotide repeat loci located on human chromosomes 2, 3, 12, and 17 have been analyzed in non-small cell lung cancer from Thai patients. Seventeen out of 30 cases (57%) harbored the microsatellite alterations. Of the 30 cases, 19 patients had a history of tobacco smoking, of whom 14 (74%) were in the group with microsatellite alterations, whereas 3 out of 11 non-smokers (26%) had these alterations. The frequency of microsatellite alterations among smokers was significantly higher than it was in non-smokers (P = 0.01 Fisher's exact test; odds ratio; 7.47).

Histology and smoking history of lung cancer cases and implications for prevention in Thailand.

BACKGROUND: Lung cancer is now a major public health problem in Thailand. This descriptive study looked at the issue of whether tumor histology varied with smoking status among lung cancer patients in Bangkok, Thailand. METHODS: A retrospective descriptive study was made of the 1,600 Thai patients with histologically proven lung cancer admitted to University of Siriraj Hospital between 1967 and 1991. Cigarette smoking histories were obtained, and histologies were classified and related to tobacco consumption. RESULTS: Overall, 78% were smokers, 72% being heavy smokers. The male to female ratio was 13:1 for smokers and 0.4:1 for nonsmokers. There were 29% squamous cell, 29% adenocarcinoma, 24% large cell, and 13% small cell carcinomas. Squamous cell carcinoma was significantly more frequent among cases with a history of smoking Thai cigarettes, which are known (from other studies) to be high in tar and nicotine, than among nonsmoking cases. Among the 350 nonsmokers, 252 of whom were female, adenocarcinoma was the most common (58%). CONCLUSIONS: The results suggest that Thai smokers can reduce their risk for lung cancer by quitting smoking, or by substituting lower tar brands. Antismoking programs should therefore be a public health priority. Given the prevalence of adenocarcinoma among nonsmokers, further work should be done to identify environmental causes.

Assessment of major carcinogenic tobacco-specific N-nitrosamines in Thai cigarettes.

This report presents new findings on the content of cancer-causing tobacco-specific N-nitrosamines (TSNA) in mainstream smoke of nine brands of commercially produced Thai cigarettes, representing about 85% of market share in Thailand. Also tested were two major and popular brands of U.S. cigarettes sold in Thailand, representing about 10% of market share. The cigarettes included filter and nonfilter cigarettes with high, moderate, and low tar and nicotine yields. The observed range for N-nitrosonornicotine (NNN) was from 28 to 730 ng/cigarette and for 4-(methylnitrosamino)-1-(3-pyridyl-1-butanone (NNK) from 16 to 369 ng/cigarette. The relatively highest TSNA values were obtained in filter and nonfilter cigarettes with high tar (22.3-28.1 mg/cigarette) and high nicotine (1.78-2.42 mg/cigarette) deliveries. The results demonstrated that there is a correlation between TSNA and tar and nicotine deliveries in mainstream smoke. The TSNA deliveries, along with the tar and nicotine levels in mainstream smoke depended on the tobacco composition. According to these results, the tar levels alone, while significant, are not a sufficient measure for the biological activity and the carcinogenic potential of cigarettes in Thailand. Consumption of tobacco products nearly quadrupled over the last three decades (1966-1995) in Thailand. Lung cancer is the leading malignancy for men and a common malignancy for women in Thailand. This report provides information that may prove helpful in evaluating the TSNA-carcinogens burden on smokers. Our goal is to offer the scientific basis for voluntary and/or government-regulated reduction of the smoke yields of TSNA in tobacco products in Thailand and in other countries.

Volatile nitrosamines and tobacco-specific nitrosamines in the smoke of Thai cigarettes: a risk factor for lung cancer and a suspected risk factor for liver cancer in Thailand.

In Thailand, smoking of commercial cigarettes and of handmade cigarettes has drastically increased in recent decades. Cancer of the lung and of the upper aero-digestive tract have also increased in Thailand as they have in many other countries. It is our working hypothesis that the increase of primary cancer of the liver, especially of cholangiocarcinoma in the north-eastern provinces of Thailand is associated with the use of tobacco in men infested with the liver fluke Opisthorchis viverrini (OV). Bioassays have shown that volatile nitrosamines and tobacco-specific nitrosamines induce cholangiocarcinoma in laboratory animals and that the hepatocarcinogenic action of nitrosodimethylamine in hamsters is significantly increased by infestation with the liver fluke OV. The endogenous formation of nitrosamines is significantly increased by OV infestation. This report presents analytical data on the concentration of volatile nitrosamines and tobacco-specific nitrosamines in mainstream smoke of nine leading brands of commercially produced Thai cigarettes which represent approximately 85% of the market share in Thailand. Observed ranges (ng/cigarette) were 8.5-31.9 for nitrosodimethylamine, 8.8-49.6 for nitrosopyrrolidine and 4.2-18.9 for nitrosodi-n-butylamine. These values are exceptionally high compared with the smoke of light and blended cigarettes from North America and Western Europe. Among the tobacco-specific nitrosamines, the range was 28-730 for nitrosonornicotine and 16-370 for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. There was a correlation between volatile and tobacco-specific nitrosamines, and tar and nicotine deliveries in the mainstream smoke. The analytical data are in line with the rate for lung cancer and support our working hypothesis that nitrosamines, and especially the tobacco-specific nitrosamines, are associated with the increased risk for primary liver cancer among those Thai people who smoke cigarettes and also carry OV infestation.