A randomised phase II study of weekly paclitaxel or vinorelbine in combination with cisplatin against inoperable non-small-cell lung cancer previously untreated.

Phase II studies have suggested that weekly paclitaxel has a higher response rate and better toxicity profile than the conventional schedule of once every 3 or 4 weeks. Our aim was to evaluate the efficacy of weekly paclitaxel plus cisplatin (PC) vs vinorelbine plus cisplatin (VC) in chemonaïve non-small-cell lung cancer (NSCLC) patients. From October 2000 to May 2002, 140 patients were enrolled. The treatment dose was P 66 mg m(-2) intravenous infusion (i.v.) on days 1, 8, and 15, and C 60 mg m(-2) i.v. on day 15, or V 23 mg m(-2) i.v. on days 1, 8, and 15, and C 60 mg m(-2) i.v. on day 15, every 4 weeks. In all, 281 cycles of PC and 307 cycles of VC were given to the patients in the PC and VC arms, respectively. There were 26 partial responses and one complete response (overall 38.6%) in the PC arm, and no complete responses, but 27 partial responses (overall 38.6%) in the VC arm. Myelosuppression was more common in the VC arm (P<0.001). Peripheral neuropathy and myalgia were significantly more common in the PC arm (P<0.001). The median time to disease progression was 6 months in the PC arm and 8.4 months in the VC arm (P=0.0344). The median survival time was 11.7 months in the PC arm and 15.4 months in the VC arm (P=0.297). We concluded that weekly PC is not suggested for NSCLC patients due to the relatively shorter progression-free survival and more common nonhaematological toxicities. British Journal of Cancer (2004) 90, 359-365. doi:10.1038/sj.bjc.6601526 www.bjcancer.com

Paclitaxel plus carboplatin, compared with paclitaxel plus gemcitabine, shows similar efficacy while more cost-effective: a randomized phase II study of combination chemotherapy against inoperable non-small-cell lung cancer previously untreated.

BACKGROUND: Paclitaxel (Taxol) plus carboplatin (PC) has shown activity in the treatment of advanced non-small-cell lung cancer (NSCLC). Non-platinum-containing combination chemotherapy, such as paclitaxel plus gemcitabine (PG), has also demonstrated reasonable efficacy. Our aim here was to evaluate the clinical efficacy and cost-effectiveness of PC versus PG in chemo-naive. advanced NSCLC patients. PATIENTS AND METHODS: Ninety (68 male, 22 female) patients were enrolled from August 1999 to August 2000. The performance status was one in 29 patients and two in 16 patients of the PC group, and one in 24 patients and two in 21 patients of the PG group. Seventeen patients had stage IIIb disease and 28 patients stage IV disease in the PC group: 18 patients had stage IIIb disease and 27 patients stage IV disease in the PG group (New International Staging System). Treatment consisted of P 175 mg/m2 and C at AUC = 7 (predicted using measured clearances and the Calvert formula) intravenous infusion (i.v.) on day 1, or P 175 mg/m2 i.v. on day 1 and G 1000 mg/m2 i.v. on days 1 and 8, every 3 weeks. RESULTS: In all, 175 cycles of PC and 184 cycles of PG were given in the PC and PG groups, respectively. The median treatment cycle was four cycles in both groups. All the patients were assessable for toxicity and response measurement. There were three complete responses and 15 partial responses (overall 40%) in the PC group, and no complete response, but 18 partial responses (overall 40%) in the PG group. WHO grades 3/4 leukopenia, anemia and thrombocytopenia occurred in six (13.3%), seven (15.5%) and five patients (11.1%) in the PC group; and in four (8.9%), six (13.3%) and 0 patients in the PG group, respectively. Two patients in each group suffered from grade 3 peripheral neuropathy. Other non-hematological toxicities were mild and few. Median survival time was 14.1 months in the PC group and 12.6 months in the PG group. One-year survival was 50.7% in the PC group and 53.3% in the PG group. The PG group had a higher total expense and expended more days undergoing treatment than the PC group (P = 0.034 and 0.069, respectively). CONCLUSIONS: Both PC and PG combination chemotherapy produce a similar efficacy in the treatment of NSCLC. However, PC is more cost-effective than PG.

Usefulness of pig-tail catheter for palliative drainage of malignant pleural effusions in cancer patients.

We retrospectively collected data from patients enrolled between 1996 and 1997, to evaluate the efficacy of sono-guided pig-tail-catheter drainage in cancer patients with large, symptomatic, amounts of malignant effusion and to evaluate the hemodynamic change after effusion drainage. A total of 477 pig-tail catheter drainage procedures were performed on 342 cancer patients. Sonographic findings, volume drained within 36 h after pig-tail insertion, heart rate and respiratory rate 24 h before and after drainage, and dyspnea sensations were recorded. We found that unilateral right-side effusion was the most frequent presentation. The mean amount of effusion drained within 36 h was 1,747 ml in cancer patients. The decreases in heart rate (from 97/min to 91/min) and in respiratory rate (from 23/min to 21/min) were both statistically significant. There was no significant correlation between the amount of effusion before drainage and the heart rate or respiratory rate. The amount drained within 36 h was correlated significantly with the changes in heart and respiratory rates. Dyspnea sensations decreased or subsided in 91% of the patients within this time period. There were few complications with the pig-tail drainage procedure. Sono-guided pig-tail drainage is a safe and convenient method of effusion drainage in cancer patients. It not only provides temporary relief of symptoms from massive pleural effusions, but can also be used for pleurodesis if needed.

A phase II trial of vinorelbine and cisplatin in previously untreated inoperable non--small-cell lung cancer.

Weekly vinorelbine injection with cisplatin had been used in treatment of non-small-cell lung cancer. We performed a phase II trial to evaluate the efficacy and toxicity of a new schedule of vinorelbine and cisplatin in patients with previously untreated, inoperable (stage IIIB or stage IV) non-small-cell lung cancer. From April 1996 to May 1997, 52 patients were enrolled for study, and 50 patients were eligible and evaluable for both response and toxicity assessment. Therapy consisted of vinorelbine, 30 mg/m2, intravenously on days 1 and 5 of a 21-day cycle, and cisplatin 100 mg/m2 (reduced to 80 mg/m2 after the first seven patients) given on day 1. A total of 211 treatment courses were administered; the median number of cycles administered per patient was 4.5 (range: 1-6), the median dose intensity for vinorelbine was 16.9 mg/m2/week (84.4%), whereas that of cisplatin was 22.8 mg/m2/week (84.7%). Twenty-five patients responded to therapy for an overall response rate of 50%; one patient attained a complete response (2%). The main toxicities were vomiting, myelosuppression, and diarrhea, which included World Health Organization grade 3 or 4 nausea/vomiting (58% patients), anemia (41% patients), neutropenia (12% patients), and diarrhea (14%). The median duration of responses was 9 months. The median time to disease progression was 6.8 months (range 0.4-18.1 months). Median survival was 13 months, and 54% of patients were alive at 1 year. We conclude that this new schedule of vinorelbine and cisplatin achieves a high response with acceptable toxicity profile in patients with advanced non-small-cell lung cancer.

A phase II study of single-agent docetaxel chemotherapy for non-small cell lung cancer.

BACKGROUND: Docetaxel is an active agent used in the treatment of non-small cell lung cancer (NSCLC). METHODS: A phase II trial of single-agent docetaxel chemotherapy was conducted in Chinese patients with NSCLC, as either a first- or second-line treatment, to assess response and toxicity. The treatment scheme was docetaxel 75 mg/m2 intravenous infusion for 1 h every 3 weeks for up to nine cycles. Dexamethasone was routinely given for 3 days, beginning 1 day before chemotherapy. RESULTS: From August 1996 to December 1997, 48 patients were enrolled, including 34 chemo-naive patients and 14 patients previously treated with one chemotherapeutic regimen. All patients were evaluable for toxicity profiles and 47 patients were evaluable for response rate. As expected, the major toxicity was myelosuppression. Grade 3 or 4 neutropenia occurred in 41 of 48 (85.5%) patients during treatment. Twenty patients (41.7%) experienced febrile neutropenia and accounted for two toxic deaths. Only one patient suffered from grade 3 thrombocytopenia and two patients from grade 3 anemia. Moderate or severe asthenia occurred in 30 patients (62.5%). Moderate fluid retention (peripheral edema) was observed in five patients (10.4%) and severe fluid retention in three; all were reversible. No grade 3 or 4 neurosensory toxicity was observed. After two cycles of treatment, 14 of 47 evaluable patients attained a partial response (29.8%, 95% CI 16.7-42.9%), including 30.3% (95% CI 14.6-46%) of those in first-line treatment and 28.6% (95% CI 4.9-52.3%) of those in second-line treatment. The median time to disease progression was 13 weeks in first-line patients and 19 weeks in second-line patients. Median survival time was 7.1 and 11.7 months in first- and second-line patients, respectively. CONCLUSION: Docetaxel is active and has an acceptable toxicity profile, in both first- and second-line treatments, in Chinese patients with inoperable NSCLC.

Tuberculous subcutaneous abscess: an analysis of seven cases.

Between 1987 and 1994, seven cases of tuberculous subcutaneous abscesses diagnosed at Veterans General Hospital, Taipei, were studied retrospectively. Three of them had associated underlying medical conditions. Multiple lesions occurred in patients with compromised immune status. Three cases were presented as tumor-like in form, and were tentatively diagnosed as chest wall tumor before mycobacterial and pathologic results were available. Except for two cases which received prolonged chemotherapy due to drug side effects or suspected drug resistance, all our cases responded well to 6 to 12 months of current antituberculosis agents. We concluded that (1) it is sometimes difficult to differentiate subcutaneous tuberculous abscess from chest wall tumor so physicians should bear in mind that tuberculosis could be the cause of such lesion, and that (2) all cases could be treated with a current chemotherapy regimen. Only a small portion of abscess needs repeated aspiration, and surgical incision and excision may not be necessary.

[Diagnostic value of ultrasonically guided lung aspiration in pneumonia].

To determine the diagnostic value of ultrasonic lung aspiration for patients with pneumonia, 60 patients with a tentative diagnosis of pneumonia were included in this study. After recording ultrasonographic findings, lung aspiration was done with a spinal needle and aspirated specimens were sent for Papanicolaou, May-Giemsa, acid fast, and Gram stains. The remaining specimens were sent for bacterial, mycobacterial and fungal culture. Twelve patients were excluded from the study because of the final diagnosis of non-infectious pulmonary diseases. In 28 cases of bacterial pneumonia, the diagnostic sensitivity of smear was 50% and culture 61%. The overall sensitivity of needle aspiration and culture was 71%. In 11 cases of bacterial pneumonia with a negative bacterial culture result, 7 cases were afebrile at the time of examination. To increase the diagnostic yield, needle aspiration should be performed at the acute stage of bacterial pneumonia. In 15 cases of pulmonary tuberculosis, the diagnostic rate of acid-fast smear was 47% and mycobacterial culture was 46%. The overall sensitivity of smear and culture was 60%. The diagnostic rate of needle biopsy was 75% and cytologic examination was 77%. Needle biopsy and cytologic examination enhanced the diagnostic rate of sputum-negative pulmonary tuberculosis. Cryptococcosis was documented by smear and needle biopsy in all of the five cases of cryptococcosis. Cryptococcosis is not easily detected by routine cytologic examination, and clinical information is still necessary to enhance the diagnostic rate. Our results show that ultrasonically guided lung aspiration is a technique with a high diagnostic yield and a low complication rate for various types of pneumonia. It is especially useful for patients without satisfactory clinical responses or without accurate microbiologic diagnosis.

Mutagenicity of particulates from the laboratory combustion of plastics.

Carcinogenic polycyclic aromatic hydrocarbons (PAHs) and nitropolycyclic aromatic hydrocarbons (nitro-PAHs) have been identified in airborne particulate organic matter extracts. The pollutant sources were generally contributed by motor vehicles and industrial activity. Massive quantities of urban solid wastes, containing plastic materials such as PVC, PET, PS, and PE, burnt in the open air in local garbage dumps are frequently found in developing countries. In this study, the smog particulates from the combustion of these synthetic polymers were produced in a laboratory combustion chamber. The mutagenicity of acetone extracts from the smog particulates was evaluated with Salmonella typhimurium TA98 and TA100 in the presence and absence of S9 mix. Four samples in TA98 exhibited higher mutagenicity than those in TA100. The greatest mutagenicity was observed from the extracts of particulates from combustion of PVC followed by that of PS, PET, and PE. To determine the major mutagenic compounds in these samples, mutagens were partially purified through TLC and their mutagenicity was monitored with TA98. 1-NP and DNPs in the above samples were also determined by HPLC. The amounts of 1-NP and DNPs generally corresponded with their mutagenicity. Higher levels of 1-NP and DNPs were generated from the combustion of PVC, PET, and PS. The combustion of synthetic polymer wastes might be responsible for the presence of high levels of 1-NP and DNPs in Taiwan urban air.

Asbestos-induced pleural fibrosis and impaired exercise physiology.

To further assess the clinical significance of asbestos-induced pleural fibrosis, we performed cardiopulmonary exercise testing in 90 subjects who were exposed to asbestos. Of the 82 subjects without an abnormal resperate exercise, 35 had normal pleura, 33 had circumscribed pleural plaques, and 14 had diffuse pleural thickening. Interstitial fibrosis (International Labor Organization [ILO]. > or = 1/10) was present in 14 of 35 subjects with normal pleura, 13 of 33 subjects with circumscribed pleural plaques, and 2 of 14 subjects with diffuse pleural thickening. Although pleural fibrosis did not appear to be related to impaired respiratory function with exercise in our entire cohort, this finding was confounded by a higher proportion of interstitial fibrosis in subjects with normal pleura. In fact, among study subjects without asbestosis, significant decreases in gas exchange (higher VD/VT and increased alveolar-arterial oxygen pressure difference) were observed at maximal exercise among subjects with pleural fibrosis. Interestingly, neither a higher respiratory rate nor a lower VT/FVC ratio was observed among those with pleural fibrosis, suggesting that the mechanical effects of pleural fibrosis on the chest wall do not explain the increased VD/VT. Using multivariate analyses to control for potential confounders, regression models showed that pleural plaques (p = 0.04) and diffuse pleural thickening (p = 0.03) were independently associated with significant increases in dead space ventilation (VD/VT) with maximal exercise. These findings indicate that asbestos-induced pleural fibrosis is independently associated with decrements in gas exchange with maximal exercise and suggest that interstitial lung disease, not detected on the routine chest x-ray film, may be responsible for this abnormal response to exercise.

The relationship between HLA-A, B, DQ, and DR antigens and asbestos-induced lung disease.

To evaluate the relationship between human leukocyte antigen (HLA) and both asbestos-induced pulmonary fibrosis and pleural fibrosis, we obtained HLA-A, B, C, DQ, and DR phenotypes in 42 long-term asbestos-exposed workers. Among these exposed workers, 15 had asbestosis (ILO > or = 1/0) on the chest radiograph and 18 had asbestos-induced pleural fibrosis. We found that there was an increased percentage of HLA-A29, HLA-B44, and HLA-Bw4 in the subjects with asbestosis. In addition, we observed a marginally positive relationship between HLA-A29 and the severity of pulmonary fibrosis. Similarly, there was a higher prevalence of HLA-DRw53 and DQ2 in the subjects with asbestos-induced pleural fibrosis. The presence of HLA-DQ2 was significantly related to the extent and type of asbestos-induced pleural fibrosis while HLA-DRw53 was not consistently related to the type or extent of pleural disease. Importantly, we observed that HLA-A29, HLA-B44, HLA-Bw4, HLA-DRw53, and HLA-DQ2 do not have a significantly shorter duration or latency of asbestos exposure. Moreover, none of the HLA haplotypes (A29, B44, Bw4, DRw53, and DQ2) that we found to be associated with radiographic manifestations of asbestos-induced lung disease were associated with the physiologic abnormalities that have been traditionally associated with asbestos-induced lung disease. The only exception was an isolated decrease in the residual volume associated with the presence of HLA-A29. These results suggest that the HLA-A29 phenotype may be associated with the development of asbestosis and the HLA-DQ2 phenotype may be associated with the development of asbestos-induced pleural fibrosis. However, these associations are not particularly strong, physiologic correlation is lacking, and previous studies do not support our findings.

Etiologic diagnosis of pulmonary infection by ultrasonically guided percutaneous lung aspiration.

Ultrasonically (US) guided percutaneous lung aspiration was performed for patients clinically diagnosed as having pneumonia (n = 18) or lung abscess (n = 16) and thus taking antibiotics. The procedure was done because of either unsatisfactory clinical or roentgenographic responses, critical underlying disease or poor general condition in the patients. Most cases with pneumonia showed hypoechoic lesion with irregular margin and typical consolidated change, while some cases showed central necrosis. Microorganisms were identified by stains in 9 cases. The overall sensitivity of needle aspiration and culture was 72.2% (13/18). Five cases failed to grow microorganism in culture, mostly due to delayed resolved pneumonia. In cases with lung abscess, the typical ultrasonographic finding was hypoechoic lesion with irregular margin associated with central necrosis or air-fluid level. The overall sensitivity for needle aspiration and culture was 81.2% (13/16). Only one case of pneumothorax was seen, which was recovered with chest intubation and oxygen inhalation. Our result showed that US-guided percutaneous lung aspiration is a technique with high diagnostic yield and low complication rate for cases with pneumonia or lung abscess.

Tuberculous subcutaneous abscesses developing during chemotherapy for pulmonary tuberculosis.

A 32-year-old woman with systemic lupus erythematosus developed military tuberculosis. Several subcutaneous abscesses infected with a strain of Mycobacterium tuberculosis susceptible to all antituberculosis drugs occurred successively during initial 1-4 months of regular antituberculosis therapy. The lung and skin lesions disappeared after continuous treatment. We emphasize that emergence of tuberculous skin lesions may occur during treatment but this does not necessarily indicate treatment failure.

Ultrasonically guided needle aspiration biopsy in the diagnosis of advanced superior vena cava syndrome.

From July 1990, 11 cases with advanced superior vena cava (SVC) syndrome were undergone ultrasonically guided needle aspiration or biopsy. Ten cases were diagnosed by thin-needle aspiration cytology. Two cases with cytologic proven lymphoma and one case without cytologic diagnosis were undergone needle biopsy, and two of them were proven to be lymphoma. The diagnostic rate of aspiration cytology was 91.0% (10/11) and of aspiration biopsy was 66.6% (2/3). The diagnostic rate of combination of aspiration cytology and biopsy was 100%. For reducing the incidence of pneumothorax, we strongly recommend this two-stage procedure that needle biopsy was performed only when cytologic diagnosis was not conclusive. Only one case developed pneumothorax in performing needle biopsy. In conclusion, ultrasonically guided needle aspiration biopsy is a safe, convenient, and high-yield diagnostic procedure for selected cases of advanced SVC syndrome.

Disseminated coccidioidomycosis with lung, skin and lymph node involvement: report of a case.

Coccidioidomycosis is a deep mycotic infection endemic to the southwestern United States. Although it has also been reported to occur in nonendemic areas, it has rarely been reported in Taiwan. We report a case of disseminated coccidioidomycosis which is the first such case reported on this island. The 28-year-old male patient developed a nonproductive cough and fever while travelling in Arizona. Chest roentgenogram revealed infiltration of the right lower lung field and enlargement of the right paratracheal lymph nodes. The titer for the complement fixation test for coccidioidin was 1:32. The patient was treated with ketoconazole for 3 months with good clinical response. However, submandibular lymphadenopathy and a macular skin lesion were noted one month after discontinuation of treatment. During hospitalization, both pathologic findings from a submandibular lymph node and a scratching smear of the skin lesion contained Coccidioides immites. The patient was put on ketoconazole again for another 6 months. Lesions on chest film were resolved and the coccidioidin complement fixation titer was gradually reduced. The patient received regular follow-up and no evidence of relapse has been seen. In this report, clinical manifestations, diagnostic methods and recent advances in the treatment of coccidioidomycosis are discussed. Because of increasing intercontinental travel and the increasing usage of immunosuppressive agents, we expect that more cases will be found in Taiwan. Keeping this disease in mind when making a differential diagnosis is the best way to make an accurate diagnosis.

Minimal inhibitory concentrations of rifabutin, ciprofloxacin, and ofloxacin against Mycobacterium tuberculosis isolated before treatment of patients in Taiwan.

Minimal inhibitory concentrations (MICs) of rifabutin, ciprofloxacin, and ofloxacin were determined for "wild" Mycobacterium tuberculosis strains, susceptible to all antituberculosis drugs in the conventional test, isolated from newly diagnosed Taiwanese patients who had never had prior treatment for tuberculosis. These MICs were within the limits previously reported for strains isolated in the United States. The range of MICs of rifabutin for Taiwanese strains was 0.015 to 0.125 micrograms/ml; ciprofloxacin, 0.25 to 2.0 micrograms/ml; ofloxacin, 0.5 to 2.0 micrograms/ml. On the basis of an evaluation of the highest broth-determined MICs found in this and in a previous study, we suggest that the following MICs, when determined in 7H12 broth radiometrically, should be used as breakpoints to classify the strain as "susceptible": for rifabutin, 0.125 micrograms/ml or less; for ofloxacin and ciprofloxacin, 2.0 micrograms/ml or less.