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

Fixed-dose combination chemotherapy (Rifater/Rifinah) for active pulmonary tuberculosis in Taiwan: a two-year follow-up.

SETTING: Veterans General Hospital-Taipei, Taiwan. OBJECTIVE: To assess the efficacy and safety of a fixed-dose combination (FDC) of Rifater (RFT)/Rifinah (RFN) in the treatment of newly diagnosed smear-positive pulmonary tuberculosis. DESIGN: Patients were randomly assigned to two 6-month short-course chemotherapy regimens. One group of patients was treated with FDCs and another was given the four component drugs (INH, RMP, EMB and PZA) as separate formulations. RESULTS: The 105 patients enrolled in the study were divided into two treatment groups. Fifty-one patients who had completed treatment without interruption, 26 in the FDC group and 25 in the separate regimen, were eligible for analysis at the end of 2 years. Among the patients with a drug susceptibility test result available, four in the FDC group had bacilli resistant to pyrazinamide. In the separate regimen group, two patients had bacilli resistant to ethambutol and six had bacilli resistant to pyrazinamide. The two regimens were of similar effectiveness with regard to sputum conversion, compliance and radiological improvement. No patient with FDC treatment developed gastointestinal symptoms, visual disturbance or peripheral neuropathy (P < 0.05). However, FDC treatment resulted in drug-induced fever in one patient. One patient (3.8%) in the FDC group relapsed 5 months after completing treatment. CONCLUSION: This study suggests that the two regimens had similar effectiveness in the treatment of smear-positive pulmonary tuberculosis. However, the fewer adverse drug events among those patients treated with the FDC regimen suggests that it has a better safety profile.

Additive effect of Interleukin-12 and Interleukin-18 on the T-helper cell pathway of malignant pleural effusion.

Interleukin-18 (IL-18) is a novel cytokine with interferon-gamma (IFN-gamma)-inducing activity, thus favoring the T-helper type 1 (Th-1) pathway. The present study attempts to define the role of IL-18 on the functions of lymphocytes isolated from malignant pleural effusions (EAL, effusion-associated lymphocytes). EAL from 10 patients with malignant pleural effusion were incubated with IL-2, IL-12, or IL-18 with/without a alpha CD3 antibody. ELISA, proliferation, and cytotoxicity assays were performed. IL-18 alone was found to have no significant effect on EAL in terms of cytokine production, lymphocyte proliferation, or cytotoxicity against tumor targets. IL-18 also had no significant additive or synergistic effect on IL-2, IL-12, or alpha CD3 co-cultured EAL. However, when IL-18 was used with IL-12, the highest IFN-gamma/IL-10 ratio was derived, suggesting that these two cytokines had an additive effect in leading EAL from the Th-2 to the Th-1 pathway. Furthermore, 1 of 5 patients' EAL had its strongest cytolytic activity against an autologous tumor when the EAL was cultured with IL-2 plus IL-18, as compared with the other 4 patients whose EAL cytolytic activity against autologous tumor was highest when using IL-2 plus alpha CD3. These findings suggest that IL-18 alone did not have a significant effect on EAL, and that IL-18 did not enhance alpha CD3's activity on EAL. However, its additive effect with IL-12 in the Th-1 pathway and with IL-2 in its cytolytic activity against an autologous tumor deserve further studies.

Pleural effusion and serum soluble fas-ligand levels are elevated in different clinical conditions.

Fas ligand (FasL) plays an important role in the regulation of apoptosis. Soluble FasL (sFasL) is produced by a cleavage of FasL from the cell surface by metalloproteinase. Whether or not sFasL exists or is elevated in the pleural effusion of different etiologies is unknown. The present study is designed to determine pleural effusion and serum sFasL levels under different clinical conditions, and ascertain if there exists a significant difference in the levels found in different clinical conditions, and whether this difference can be used as a tool for differential diagnosis. Soluble FasL levels in the pleural effusion and serum of 103 patients, including 37 with malignant pleural effusion, 24 with uncomplicated parapneumonic effusion, 8 with bacterial empyema, 16 with tuberculous pleurisy, and 18 with transudate effusion (8 with congestive heart failure and 10 with viral liver cirrhosis), were analyzed with ELISA assays. Pleural effusion from patients with bacterial empyema (median 79.4 pg/ml) and TB pleurisy (median 31.9 pg/ml) contained significantly higher amounts of sFasL than the pleural effusion from all other conditions studied (p <0.001). Viral liver cirrhosis had a significantly higher serum sFasL level (median 53.6 pg/ml, p = 0.025, when compared with other patients). Patients with congestive heart failure had the lowest serum sFasL levels when compared with other patients (p = 0.014). There was no significant correlation between pleural effusion sFasL levels and other parameters, such as effusion LDH, cell count, neutrophil, and lymphocyte percentage. In conclusion, soluble FasL is a useful marker for the differentiation of bacterial empyema and TB pleurisy from other disease entities. In addition, the elevation of serum sFasL levels in viral liver cirrhosis can also be used to differentiate cirrhosis from congestive heart failure, in which both effusions are transudate.

Gemcitabine and cisplatin in a multimodality treatment for locally advanced non-small cell lung cancer.

The role of new cytotoxic agents like gemcitabine has not yet been proven in the neoadjuvant settings. We designed a phase II study to test the feasibility of using gemcitabine and cisplatin before local treatment for stage III non-small cell lung cancer patients. Patients received three cycles of induction chemotherapy of gemcitabine (1000 mg m(-2), days 1, 8, 15) and cisplatin (90 mg m(-2), day 15) every 4 weeks before evaluation for operability. Operable patients underwent radical resection. Inoperable patients and patients who had incomplete resection received concurrent chemoradiotherapy with daily low dose cisplatin. All patients who did not progress after local treatment received three more cycles of adjuvant chemotherapy of gemcitabine and cisplatin. Fifty-two patients received induction treatment. Two patients had complete response and 31 patients had partial response (response rate 63.5%) after induction chemotherapy. Thirty-six patients (69%) were operable. Eighteen patients (35%) had their tumours completely resected. Two patients had pathological complete response. Median overall survival was 19.1 months, projected 1-year survival was 66% and 2-year survival was 34%. Three cycles of gemcitabine and cisplatin is effective and can be used as induction treatment before surgery for locally advanced non-small cell lung cancer patients.

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.

Life-threatening hypersensitivity pneumonitis induced by docetaxel (taxotere).

4 patients with advanced non-small-cell lung cancer (NSCLC) treated with docetaxel developed life-threatening pneumonitis requiring mechanical ventilation. Docetaxel (30-60 mg x m(-2), according to a different protocol) was infused within one hour with standard premedications. One patient's pneumonitis occurred 5 days after the first dose of docetaxel, and that of the other 3 between the 2nd and 6th cycles. Based on the clinical course, radiological findings of an interstitial pneumonitis, and exclusion of other possible resultant causes, including metastatic cancer, radiation pulmonary injury, infection, or connective tissue disease, hypersensitivity pneumonitis was diagnosed. The patients were treated with hydrocortisone at 1200 mg per day or methylprednisolone at 240 mg per day. Although 3 of the 4 had a partial improvement in lung oxygenation, all patients' conditions of hypersensitivity pneumonitis persisted and were complicated by other events, such as hospital-acquired infection and tension pneumothorax. The presence of this unusual hypersensitivity pneumonitis, which was so severe as to be life-threatening and refractory to high-dose corticosteroid therapy, should be taken into account during docetaxel treatment.

Interleukin-7 and interleukin-12 have different effects in rescue of depressed cellular immunity: comparison of malignant and tuberculous pleural effusions.

The present study attempts to determine the role of interleukin-7 (IL-7) and IL-12 in recovering the functions of the lymphocytes of malignant effusion, in terms of cytokine production, proliferation, and cytolytic activity, compared with lymphocytes from tuberculous pleural effusion. Effusion-associated lymphocytes (EAL) were isolated from tuberculous (tEAL) and malignant (mEAL) pleural effusions. The EAL proliferate response was measured after 3 days in culture. Interferon-gamma (IFN-gamma) production and cytotoxicity against K-562 cells or autologous tumor cells were assessed after 6 days in culture. It was found that the mEAL had depressed proliferation, IFN-gamma production, and cytolytic activity, as compared with tEAL. Stimulation with IL-12 plus IL-2, but not with IL-7 plus IL-2, fully restored the IFN-gamma production of mEAL to that of tEAL levels. In contrast, the proliferate response of mEAL was enhanced significantly more with IL-7 plus IL-2 than with IL-12 plus IL-2. Both the IL-7 plus IL-2 and IL-12 plus IL-2 stimulation of mEAL showed a significant increase in cytolytic activity against autologous tumor cells, although the cytolytic activity against K-562 cells did not increase. These results suggest that tEAL had a higher cellular activity than mEAL. This depressed cellular function of mEAL could be reversed with cytokines. However, different cytokines had different effects on mEAL; for example, IL-7 had a better effect in the stimulation of lymphocyte proliferation compared with IL-12, which had a better effect in driving the lymphocytes to the T helper 1 (TH1) pathway and a higher IFN-gamma production. Both IL-7 and IL-12, in the presence of IL-2, can restore the immunosuppressed cytolytic activity of the lymphocytes of malignant pleural effusion against autologous tumor.

Hepatocellular carcinoma with Pancoast's syndrome as an initial symptom: a case report.

Pancoast's syndrome refers to a condition consisting of Horner's syndrome and arm pain that is most commonly found in patients with a lung tumor of the superior sulcus invading the upper ribs or spine, lower brachial plexus and sympathetic chain. We report a 76-year-old female who had a thoracic inlet mass that presented as Pancoast's syndrome, showing profound pain, numbness and weakness of the left upper limb. Further evaluation revealed an increased level of serum alpha-fetoprotein (24278 ng/ml), cryptogenic liver cirrhosis and primary hepatocellular carcinoma with protruding T3 vertebra metastasis that resulted in Pancoast's syndrome. To our knowledge, it is a rare case and only one case has been reported previously.

Utility of PCR assays for rapid diagnosis of BCG infection in children.

We report Mycobacterium bovis BCG infection in two children vaccinated with BCG (Tokyo strain) on the first day of life. Their diagnoses were made by biopsy of skin lesions and pus from an anterior chest wall abscess, respectively, yielding a positive culture of mycobacteria fully susceptible to rifampicin, isoniazid and ethambutol, but resistant to pyrazinamide. M. bovis BCG was identified by a negative niacin test, absence of nitrate reductase and resistance to pyrazinamide and cycloserine. The diagnoses were further confirmed by a combination of an allele-specific polymerase chain reaction ated strain of Mycobacterium bovis, is the only available vaccine for the prevention of tuberculosis. Although complications are rare after BCG vaccination and the outcome is usually favourable, serious BCG infections can occur. We report two cases of M. bovis BCG infection in children, a 4-year-old immunocompetent girl and an 8-month-old immunodeficient boy. To our knowledge, this is the first report of BCG complications in children in which two recently developed polymerase chain reaction (PCR) based methods were used for rapid identification of M. bovis BCG infection. (PCR) and a multiplex PCR method. Based on the drug susceptibility results, treatment with rifampicin, isoniazid and ethambutol was instituted. One patient (Case 1) improved clinically and is well after treatment. However, the other patient with severe combined immunodeficiency died of disseminated BCG infection in spite of intensive anti-tuberculosis therapy. Although BCG is considered to be a safe vaccine, it should be kept in mind that complications related to BCG do occur.

An analysis of cytokine status in the serum and effusions of patients with tuberculous and lung cancer.

The present study was designed to ascertain whether or not the pleural effusion and serum cytokine levels (granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin-10 [IL-10], and interferon-gamma [IFN gamma]) in lung cancer patients differ from tuberculous (TB) pleural effusion, in which a strong cellular immune reaction is found; and, whether cytokine levels are a prognostic factor in lung cancer patients with malignant effusion. A total of 202 lung cancer patients with malignant pleural effusion and 26 patients with TB pleural effusion were studied consecutively between 1995 and 1998. Serum and effusion cytokine levels were analyzed with ELISA assays. The results showed that pleural effusion GM-CSF and IL-10 levels were significantly higher than serum levels in both cancer and TB patients. Pleural effusion IFN gamma levels were significantly higher than serum levels in TB patients. IFN gamma levels in both pleural effusion and serum were significantly higher in TB patients than in those with cancer. No significant difference was found, between TB and cancer patients, in the serum or pleural effusion levels of either IL-10 or GM-CSF. The ratio of pleural effusion IFN gamma to serum IFN gamma, effusion IFN gamma to effusion IL-10, and effusion IL-10 to serum IL-10, were all significantly higher in TB than in cancer patients, suggesting a higher cellular activity and T-helper 1 (Th1) reaction in TB pleural effusion than in malignant effusions, which were predominantly Th2 type. Survival analysis showed no significant difference in lung cancer patients with different levels of these cytokines. It was concluded that lung cancer patients with malignant pleural effusion had poorer immune profiles than those with TB pleurisy, both locally and systemically; and the cytokine profiles were not prognostic factors for lung cancer patients with malignant pleural effusion.

Childhood tuberculosis presenting as an anterior chest wall abscess.

Chest wall abscess is a rare manifestation of childhood tuberculosis. We report a case of a tuberculous chest wall abscess in a 4-year-old healthy girl who had received Bacillus Calmette-Guerin (BCG) vaccination at birth. She developed a localized anterior chest wall mass, which was initially mistaken for enchondroma on the chest radiograph. Pathologic examination of the biopsy specimen revealed chronic granulomatous inflammation and positive acid-fast staining, which confirmed the diagnosis of chest wall tuberculosis infection. She received a 12-month course of anti-tuberculous treatment and was perfectly well 1 year later. The chest wall lesion resolved without the need for surgery. In conclusion, tuberculosis should be excluded in children with undiagnosed chest wall lesions, especially in endemic areas, even if they have been vaccinated with BCG. Adequate anti-tuberculosis treatment can result in a complete recovery.

Prognosis and recurrent patterns in bronchioloalveolar carcinoma.

STUDY OBJECTIVE: Bronchioloalveolar carcinoma (BAC) is an uncommon pulmonary neoplasm with various radiologic and clinical presentations. In this article, we analyze the initial radiologic findings, TNM stagings, surgical types, and radiologic features of recurrence, and correlate them with patient survival. DESIGN: A retrospective review of 93 patients who underwent resection for BAC from February 1989 to May 1999. PATIENTS: There were a total of 153 patients with BAC diagnosed during this period. Among them, 60 patients (39.2%) had diffuse disease and received medical therapy only, and the remaining 93 patients (60.8%), who had localized disease, underwent surgical resection. Patients who received surgical resection were enrolled in this study. MEASUREMENTS: Data regarding demographics, presentation symptoms, initial radiologic features, surgical type, tumor staging, recurrence status, radiologic patterns of recurrence, and survival were obtained from all patients. RESULTS: Female patients were significantly younger than male patients. Patients who were female, nonsmoking, undergoing curative surgery, lobectomy, or bilobectomy, and with early tumor staging and no nodal involvement had a better prognosis. Patients with a right lung tumor had a longer survival than those with a left lung tumor, with borderline significance. Among those who suffered from recurrent diseases, a second resection yielded a better survival. Multivariate analysis showed curative surgery, initial surgical type, recurrence status, radiologic patterns of recurrence, and duration from surgical resection to recurrence all had a significant impact on survival. CONCLUSIONS: Those patients with localized, early-stage BAC who underwent curative surgery had a better survival. Patients with localized recurrence after the initial surgery warranted a second resection. Those with a diffuse radiologic pattern of recurrence and/or early recurrence had a worse prognosis.

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.

Combination chemotherapy with tamoxifen, ifosfamide, epirubicin and cisplatin in extensive-disease small-cell lung cancer.

BACKGROUND: A study of tamoxifen, ifosfamide, epirubicin and cisplatin (TIEP) chemotherapy was conducted in patients with extensive-disease, small-cell lung cancer (SCLC) to assess response and toxicity. METHODS: From November, 1997, to February, 1999, 11 patients were treated, including six chemo-naïve patients and five patients previously treated with cisplatin plus etoposide (EP). The treatment regimen included tamoxifen 60 mg twice daily orally on days 1 to 3, ifosfamide 3 g/m2 intravenous (i.v.) infusion for 60 minutes with mesna on day 2, epirubicin 50 mg/m2 i.v. bolus on day 2 and cisplatin 60 mg/m2 i.v. for 60 minutes on day 2, every 4 weeks for up to six cycles. RESULTS: All patients were evaluated for toxicity and response rate. As expected, the major toxicity was myelosuppression. Grade 3 or 4 leukopenia or neutropenia occurred in all patients during treatment. Two patients (18.2%) experienced fever in association with the neutropenia, one of whom died of sepsis. Grade 3 anemia occurred in two patients (18.2%) during treatment. Toxicities other than neutropenia and anemia were limited. After two cycles of treatment, five of six chemo-naïve patients (83%), and one of five previously treated patients (20%) attained a partial response (overall 54.5%, 95% confidence interval 25%-83.9%). Median survival time was 8.5 and 6 months in chemo-naïve and previously EP-treated patients, respectively. The response rate and median survival time in chemo-naïve patients did not improve compared with a previous study of ifosfamide plus etoposide undertaken 4 years earlier. CONCLUSIONS: Although TIEP is an active combination regimen with an acceptable toxicity profile in Chinese patients with extensive-disease SCLC, it showed no remarkable benefit compared with other regimens used in chemo-naïve patients. The 20% response rate and median survival of 6 months in EP-treated patients deserve further study.

Prognostic role of pericardial fluid cytology in cardiac tamponade associated with non-small cell lung cancer.

BACKGROUND AND STUDY OBJECTIVES: Cardiac tamponade is a life-threatening complication of non-small cell lung cancer (NSCLC). Malignant pericardial effusion signifies advanced disease, but the significance of a negative pericardial fluid cytology in patients with advanced lung cancer is still controversial. The differential diagnosis of cytology-negative pericardial effusion is difficult and sometimes impossible. The purpose of this study is to determine the prognostic role of pericardial fluid cytology in patients with NSCLC and cardiac tamponade. DESIGN: Retrospective review of patients with concurrent NSCLC and cardiac tamponade over a 10-year period. METHODS AND RESULTS: Eighty-two patients were included in this study. Pericardial fluid cytology was positive in 60 patients and negative in 22 patients. The overall median survival was 74.5 days, and 1-year survival was 7.3%, with no survival difference between the two groups (p = 0.2506). However, there was a significant survival difference after different treatment strategies. Patients receiving systemic chemotherapy survived longer than those receiving local therapy (p<0.001), and these patients, in turn, survived longer than those receiving supportive treatment (p<0.001). CONCLUSIONS: When patients have concurrent advanced NSCLC and cardiac tamponade, the most likely cause of the pericardial effusion is the cancer itself, regardless of the results of the cytologic examination. Our results suggest that systemic chemotherapy might prolong survival in such patients, but further prospective, randomized study is necessary.

Phase II study of tamoxifen, ifosfamide, epirubicin and cisplatin combination chemotherapy in patients with non-small cell lung cancer failing previous chemotherapy.

We conducted a phase II study of tamoxifen, ifosfamide, epirubicin, and cisplatin (TIEP) chemotherapy in patients with non-small cell lung cancer (NSCLC) who had failed previous chemotherapy, in order to assess the response and toxicity of TIEP. Between November 1997 and May 1999, 25 patients were treated. Twelve of the 25 patients (48%) had been previously treated with cisplatin-based combination chemotherapy. TIEP doses were tamoxifen 60 mg oral twice daily on days 1-3; ifosfamide 2.4 g/m(2) intravenous infusion (IV) 60 min with mesna on day 2; epirubicin 40 mg/m(2) IV bolus on day 2; and cisplatin 50 mg/m(2) IV 60 min on day 2 every 4 weeks for up to six cycles. Seventy one cycles were given to 25 patients, with a median of three cycles (range one to six cycles). All patients were evaluable for toxicity profile and response rate. As expected, the major toxicity was myelosuppression. Grade 3 or 4 neutropenia occurred in 15 patients (60%) during treatment, as well as in 31% of the total courses. Febrile neutropenia occurred in two patients. No toxic death occurred in this study. Grade 3 thrombocytopenia occurred in five patients with five cycles. Toxicities other than myelosuppression were few and mild in severity. After two cycles of treatment, five of 25 patients (20%) had a partial response (95% confidence interval 4.3-35.7%). Among 12 patients previously treated with cisplatin-based chemotherapy, three patients (25%) achieved a partial response. The median time to disease progression was 4.9 months and median survival was 7.7 months. The response rate and median survival were better than in our previous study of salvage chemotherapy with ifosfamide, 5-FU, and leucovorin; and with ifosfamide, epirubicin, 5-FU, and leucovorin. In conclusion, TIEP appears to be an active combination regimen with an acceptable toxicity profile in Chinese patients with NSCLC who have failed previous chemotherapy.

Treatment of non-small-cell lung cancer: the Chinese experience in a general teaching hospital.

BACKGROUND: It has been reported that combination chemotherapy and radiotherapy prolongs locally advanced stage IIIB non-small-cell lung cancer (NSCLC) patient survival and cisplatin-based chemotherapy prolongs survival in stage IV disease. This study was aimed at investigating whether this conclusion also applies to Chinese patients. METHODS: We retrospectively reviewed the medical records of NSCLC patients diagnosed at the Taipei Veterans General Hospital covering a period from 1990 to 1996 to examine the effect of treatment regimen on survival. RESULTS: There were 3,925 cases of NSCLC diagnosed during this period. The stage at diagnosis was stage III or IV in the majority (76.6%) of cases. Surgery followed by chemotherapy with or without radiotherapy conferred a survival benefit of more than two years in stage IIIA patients. For stage IIIB patients, chemotherapy in combination with radiotherapy yielded a median survival of 13 months, compared to only seven months for radiotherapy alone. For stage IV patients, cisplatin-based chemotherapy prolonged median survival for more than two months compared with palliative radiotherapy alone or supportive care only. Survival was improved in stage IV patients who received chemotherapy during 1990 to 1996 compared with those who received chemotherapy during 1985 to 1989. This improvement was most likely due to improvements in supportive care because the treatment regimen was constant during the study period. CONCLUSIONS: Cisplatin-based chemotherapy prolonged survival of Chinese patients with metastatic NSCLC. Combination chemotherapy and radiotherapy also prolonged survival of Chinese patients with locally advanced NSCLC.

Combination versus alternating chemotherapy in small-cell lung cancer.

BACKGROUND: The major obstacles in the treatment of small-cell lung cancer (SCLC) are tumor recurrence and the emergence of drug resistance to chemotherapeutic agents. Using alternating non-cross-resistant combination regimens is an attractive strategy, but the efficacy and toxicities are still controversial. METHODS: Previously untreated SCLC patients were randomly assigned to standard CEOV therapy (cyclophosphamide, epirubicin, vincristine = oncovin, and etoposide = VP-16) or CEOV alternating with CAM therapy (cyclophosphamide, ACNU and methotrexate). Chemotherapy was repeated every 4 weeks for a total of eight cycles. Complete and partial responders were administered thoracic irradiation. RESULTS: Between July 1987 and July 1993, 150 patients were enrolled and 123 were evaluable. There was no significant superiority in the treatment outcome for CEOV-CAM therapy over CEOV therapy in terms of overall response rate (51% vs 71%), complete response rate (9% vs 35%), median survival time (9.5 months vs 12.0 months) and 2-year survival rate (7% vs 13%). Both patients with limited disease and extensive disease had equal response rates to the CEOV regimen (70% and 71%, respectively). However, patients with limited disease had a significantly higher response rate to the CEOV-CAM regimen than did patients with extensive disease (65% vs 36%, p = 0.04). Toxicities for both treatment arms were comparable. Patients who achieved complete or partial response received thoracic irradiation and had significantly longer survival than responders who did not receive thoracic irradiation (14.0 months vs 12.0 months, p = 0.02). There were equal chances of tumor recurrence in the chest and at distant sites (66% vs 67%) in the CEOV arm. However, in the CEOV-CAM arm, tumors were more likely to occur in the chest than in distant sites (86% vs 36%) (p = 0.0016). CONCLUSIONS: We concluded that alternating chemotherapy provides no therapeutic advantage compared with four-regimen combination chemotherapy in terms of tumor response, median survival and 2-year survival rate for SCLC patients. Early thoracic irradiation should be applied to achieve better local control and less distant recurrence for chemotherapy responders.