Efficacy and tolerability of irinotecan in patients with advanced colorectal cancer in Singapore.

INTRODUCTION: Colorectal cancer is the commonest malignancy encountered in Singapore. The long-term outcome of patients with advanced diseases is poor. For many decades, 5-fluorouracil was the only effective cytotoxic drug against colorectal cancers. Randomised trials have documented the efficacy of irinotecan in patients with metastatic colorectal cancer. We investigated the efficacy and safety profile of irinotecan (CPT-11), as a second-line treatment for an Asian population who had failed 5-fluorouracil-based chemotherapy. MATERIALS AND METHODS: A total of 33 patients were enrolled in the study between October 1996 and May 1999. This was an open label phase II study. All patients who had received at least one dose of CPT-11 were evaluated for toxicity. Thirty patients were evaluated for response. RESULTS: Six patients (20%) had partial responses and 1 (3%) experienced minor response. Fourteen patients (47%) progressed. Nine patients (30%) had stable disease. The range of time to progression was 5.8 months to 21 months. The median survival was 9.5 months. There was no treatment-related death. Seven patients (23%) who received treatment had diarrhoea. Only 2 of the 7 patients had grade 3-4 diarrhoea. Eleven patients (37%) suffered from haematological toxicity, of whom 2 patients had grade 3-4 neutropenia. CONCLUSION: We demonstrated efficacy and tolerability of CPT-11 in Singaporean patients with advanced colorectal cancer.

Concurrent chemoradiotherapy followed by adjuvant chemotherapy in Asian patients with nasopharyngeal carcinoma: toxicities and preliminary results.

PURPOSE: Nasopharyngeal carcinoma (NPC) is endemic in Singapore. Nearly 60% of the patients diagnosed with NPC will present with locally advanced disease. The North American Intergroup study 0099 reported improved survival outcome in patients with locally advanced NPC who received combined chemoradiotherapy when compared to radiotherapy alone. Hence we explored the feasibility and efficacy of a similar protocol in our patients. METHODS AND MATERIALS: Between June 1996 and December 1997, 57 patients were treated with the following schedule as described. Radical radiotherapy (RT) of 66-70 Gy to the primary and neck with cisplatin (CDDP) 25 mg/m2 on days 1-4 given by infusion over 6-8 hours daily on weeks 1, 4, and 7 of the RT. This is followed by a further 3 cycles of adjuvant chemotherapy starting from week 11 from the first dose of radiation (CDDP 20 mg/m2/d and 5-fluorouracil [5-FU] 1 gm/m2/d on days 1-4 every 28 days). RESULTS: The majority of patients (68%) had Stage IV disease. About 54% of patients received all the intended treatment; 75% received all 3 cycles of CDDP during the RT phase and 63% received all three cycles of adjuvant chemotherapy. The received dose intensity of CDDP and 5-FU of greater than 0.8 was achieved in 58% and 60% of the patients respectively. Two treatment-related deaths due to reactivation of hepatitis B and neutropenic sepsis respectively, were encountered. At median follow-up of 16 months, 14 patients had relapsed, 12 systemically and 2 loco-regionally. CONCLUSION: Due to the acceptable tolerability of such a protocol in our cohort of patients, we have embarked on a Phase III study to confirm the results of the 0099 Intergroup study in the Asian context.

Vinorelbine, ifosfamide and cisplatin in advanced non-small cell lung cancer.

Between September 1994 and July 1997, 78 patients with advanced/metastatic, non-small cell lung cancer (NSCLC) were selected for the NIP (vinorelbine, ifosfamide, and cisplatin) protocol. The study group included 43 males; age range 34-74 years; median age 56 years; median follow-up for all patients was 14 months and for surviving patients, 30 months. Histological distribution included 55 adenocarcinomas (70.5%), 8 squamous cell carcinomas, and 9 large cell carcinomas. Stage distribution was 14 stage IIIB (malignant effusions) and 64 stage IV or recurrent metastatic; sites of metastasis were lungs, -26; liver-19; bones-27; brain-7; adrenals-3; distant nodes-2; skin-2. The NIP regimen was well tolerated by most of the patients but nausea/vomiting was noted in 55% of the cycles administered, most of them of grade 1-2 severity. Fifteen neutropenic episodes (5%) were encountered. Response to NIP was: 44 partial responses (56%); 1 complete response (1%); overall response, 58%. For stage IIIB, overall response was 36%, while for stage IV/metastatic, overall response was 63%. The median time to progression was 7 months for stage IIIB and 8 months for stage IV/metastatic disease and the overall median survival achieved was 14 months, with 60% of patients alive after one year. No significant difference in survival outcome was noted between patients with metastatic disease and those with stage IIIB (malignant effusion) disease. The NIP regimen has produced encouraging results in advanced NSCLC, as well as a favourable toxicity profile. The efficacy of NIP as a palliative tool should be assessed. A randomized trial to compare NIP with a two-drug combination of vinorelbine and cisplatin has been initiated.

Induction chemotherapy followed by concurrent chemoradiotherapy in stage III unresectable non-small cell lung cancer.

The favourable experience with the combination regimen of vinorelbine, ifosfamide and cisplatin (NIP) in patients with metastatic non-small cell lung cancer (NSCLC) has led to a protocol assessing this regimen as an induction treatment in patients with stage III unresectable NSCLC, followed by thoracic radiotherapy with concurrent daily cisplatin as a radiosensitizer. Two cycles of NIP were administered 21 days apart; each cycle comprised i.v. vinorelbine 25 mg/m2 on days 1 and 8, i.v. ifosfamide 3 g/m2 on day 1 with MESNA as uroprotection, and i.v. cisplatin 50 mg/m2 on day 1. Radical thoracic radiotherapy commenced on day 43 to a total dose of 64 Gy and i.v. cisplatin 6 mg/m2 was given concurrently prior to each fraction of radiation as a sensitiser. Two more cycles of NIP were given to patients who responded favourably to the induction treatment about 2 weeks after completion of radiation. Between July 1995 and July 1997, 44 patients were treated with this protocol. This treatment schedule was generally well tolerated. Grade 3-4 neutropenia occurred in 50% of the patients and neutropenic sepsis was seen in 8. Grade 3-4 oesophagitis was uncommon. Most of the patients were able to complete the induction and concurrent chemoradiotherapy phase. Major response occurred in 75% of the patients with 2 (4.5%) complete responses (CR). A total of 6 patients achieved CR after chemoradiotherapy. At a median follow-up of 35 months, the median overall survival for all patients was 15 months with a 3-year survival rate of 24%. The median overall survival for stage IIIA patients was 19 months with a 3-year survival rate of 39% in contrast to 13 months' median overall survival and only 15% 3-year survival rate for stage IIIB. The NIP regimen results in a high response rate in NSCLC and this treatment programme seems to benefit selected patients with stage III disease.

Mitomycin, ifosfamide and cisplatin in advanced non-small cell lung cancer.

BACKGROUND: Chemotherapy can be used to palliate the symptoms in patients with advanced non-small cell lung cancer. PATIENTS: Twenty-four chemo-naive patients with stage IIIB and IV non-small cell lung cancer were treated with the MIC regimen (mitomycin, ifosfamide and cisplatin). RESULTS: The overall response rate was 33% (partial response) and median duration of response was 7 months (range 5 to 10 months). At median follow-up of 26 months, the median survival was 8 months, and 1-year survival was 29%. Toxicities were tolerable. CONCLUSION: This appears to be a reasonable regimen for palliating advanced non-small cell lung cancer.

Activity of paclitaxel by three-hour infusion in Asian patients with metastatic undifferentiated nasopharyngeal cancer.

BACKGROUND: Despite its moderate anti-tumour activity in head and neck cancers there have been no reports on the activity of paclitaxel in patients with nasopharyngeal cancer, a highly chemosensitive tumour. A phase II study was thus initiated to determine the objective response rate and toxicity of paclitaxel in patients with previously untreated metastatic nasopharyngeal cancer. PATIENTS AND METHODS: Twenty-four patients with previously untreated measurable metastatic nasopharyngeal carcinoma were accrued, one of them ineligible because of concomitant beta-blocker usage. Male:female ratio was 19:5, with a median age of 46 years. All had previously received radiotherapy but were chemotherapy-naïve. The great majority (20 of 24) had undifferentiated carcinoma. Paclitaxel (Anzatax, Faulding Pharmaceuticals) 175 mg/m2 was given intravenously over three hours every 21 days after premedication with oral dexamethasone and intravenous diphenhydramine and cimetidine. RESULTS: There were five (21.7%) partial responses while eight patients remained stable. Median response duration was 7.5 months and median survival was 12 months. The main toxicity was haematological, with grade 1-2 neutropenia in 19% and grade 3-4 neutropenia in 4.5% of cycles. Three cycles were complicated by grade 3-4 anaemia and one patient required a blood transfusion. No thrombocytopenia was seen. Peripheral neuropathy was frequent (20 of 23 patients) but mild. Alopecia was complete in 14 patients. There were no cardiac toxicity or hypersensitivity reactions. CONCLUSIONS: Paclitaxel is well tolerated even in previously irradiated patients with metastatic nasopharyngeal cancer. Single-agent activity was 22% and its inclusion into combination chemotherapy regimens should be studied.

Use of ondansetron in the control of emesis in autologous peripheral blood stem cell transplant (APBSCT) for solid tumours.

AIM: The use of autologous peripheral blood stem cell transplant (APBSCT) for solid tumours have increased exponentially in the last 5 years. While the use of 5-hydroxytryptamine 3 (5HT3) receptor antagonists has been shown to improve control of emesis in patients receiving conventional dose chemotherapy, similar literature in APBSCT is more limited. We report our experience in the use of ondansetron in APBSCT. METHOD: Twenty-three patients with solid tumours receiving high-dose chemotherapy with APBSCT were studied. All were started on intravenous ondansetron at 24 mg/day before commencement of the conditioning regimen and continued till vomiting had ceased for 24 hours. The conditioning regimen used was dependent on the tumour type and the duration ranged from 4 to 6 days. Control of emesis was assessed by the number of vomiting episodes in each 24-hour period, monitored throughout conditioning till discharge from hospital. RESULTS: Complete or major protection from vomiting was achieved in 83% of patients on day 1. During the entire conditioning period, 52% of patients achieved complete or major response to ondansetron. After the conditioning period (delayed emesis), 44% of patients achieved complete or major response. CONCLUSIONS: The control of emesis for patients undergoing high-dose chemotherapy with APBSCT is fair with ondansetron. Research on more effective combinations to further improve emetic control in this selected group of patients is needed.

Adjuvant chemotherapy for patients with resected Dukes' C and high-risk B2 colon cancer with fluorouracil and levamisole.

Carcinoma of the large bowel is the second leading cause of cancer mortality in Singapore. Although the great majority of patients are discovered at a stage where resection with curative intent is possible, almost half of the patients afflicted will die of it. The combination of 5-fluorouracil + levamisole used in patients with curatively resected high risk Dukes B2 and all Dukes' C colon cancers has been shown to reduce cancer recurrence rate and improve overall survival. Since 1990 adjuvant chemotherapy has been recommended for this group of patients. This report describes patients treated in Singapore, their toxicities and their outcome. A total of 341 patients were treated between 1990 and 1996. Treatment compliance was 71.8%. Toxicity was moderate with mainly grade 1-2 nausea and vomiting, diarrhoea, stomatitis, alopecia, and neutropenia. There was 1 treatment-related death. Median recurrence-free interval was 81 months and median survival was not reached at 90 months. This regimen is tolerable. Until further randomised reports comparing 5-fluorouracil + levamisole to other combinations are available, this combination chemotherapy is recommended to patients after surgical resection of the high risk Dukes' B2 and Dukes' C colon cancer to reduce cancer recurrence and improve overall survival.

Primary pulmonary lymphoma--clinical review from a single institution in Singapore.

Primary pulmonary lymphoma is a rare and vexing subset of extranodal non-Hodgkin's lymphoma. We report 11 cases and provide a brief literature review. We also highlight an unusual case of a relapsed peripheral T-cell primary lung lymphoma that underwent apparent spontaneous remission. Eleven cases of primary pulmonary lymphoma treated in our institution were studied for their clinical characteristics, behaviour, response to treatment and clinical outcome. The median duration of follow up was 26 months. The mean age was in the 50s and the presenting symptoms generally respiratory and non-specific. LDH levels did not correlate with either stage or grade of disease. Lower lobe involvement was most common and nodules and mass-like lesions the main radiologic feature. Small lymphocytic lymphoma accounted for the majority of cases and were indolent in behaviour. Good symptom control and radiologic response was achieved with chemotherapy in disseminated low grade lung lymphomas. Combination chemotherapy was effective in the aggressive lymphomas. In conclusion, Small lymphocytic lymphoma of the lung is an indolent disease with a long symptom-free survival even after recurrence. Our series confirms the clinical characteristics of primary pulmonary lymphoma. The role of Ling Zhi in effecting the spontaneous remission in the peripheral T-cell lymphoma is speculative.

Phase I study of immunotherapy of cutaneous metastases of human carcinoma using allogeneic and xenogeneic MHC DNA-liposome complexes.

The generation of strong tumor-specific immunity by in situ gene therapy is an attractive approach for the eradication of human cancer lesions. The objectives of this study were to examine the toxicities of employing the human HLA-A2, HLA-B13 and the murine H-2K genes to generate tumor regression in patients with different cancer types via DC-Chol/DOPE cationic liposomes. The study was composed of two phaseI/II trials involving a total of 19 late-stage cancer patients. The patients were given four weekly injections of a DNA-liposome mixture directly into a cutaneous nodule. These procedures resulted in no significant clinical side-effects. The HLA-A2 gene gave the highest level of expression in situ. Although all patients treated had progressive systemic disease and eventually succumbed to their disease, strong local responses were generated in the treated nodules. Of the eight patients whose cutaneous nodules received HLA-A2 DNA, two completely regressed while four tumor nodules gave a partial local response. All but one of the patients who received HLA-A2-liposome mixtures and had a subsequent local response were either cervical or ovarian carcinoma patients. This local response, seen in a group of patients who had relapsed stage IV systemic metastatic disease and were refractory to all available therapies, demonstrates the generation of a strong local immune response following our in situ gene therapy protocol. Further studies to investigate the use of HLA-A2 DC-Chol/DOPE cationic liposomes for immunotherapy of cervical and ovarian cancers are warranted.

Usefulness of bacteriologic cultures in choice of antibiotics in patients with chemotherapy-induced neutropenic sepsis.

Neutropenic sepsis is a potential problem in cancer patients undergoing cytotoxic chemotherapy. Septic work-up including cultures from various sites is routinely done for these patients. To assess the usefulness of these cultures, a retrospective review of all patients admitted for neutropenic sepsis in the period from June 1994 to August 1995 was conducted. All patients included in the study had solid tumours which were being treated at our institution during the study period. All had fever and documented neutrophil count of < 1 x 10(9)/l on at least one occasion. There was a total of 41 patients with 52 episodes of neutropenic sepsis. Of the 52 episodes, there were positive cultures in 14 (27%) episodes, including 7 from blood, 2 from urine and 5 from skin. In the bacteriologic cultures, gram-negative bacteria were isolated in 11 episodes and gram-positive bacteria in 5 episodes (2 episodes had both gram-negative and gram-positive bacteria isolated, and 1 episode had two gram-negative bacteria). Majority of the patients (96%) were treated with a third generation cephalosporin with/without an aminoglycoside. This empirical treatment was effective with resolution of fever in 39 (75%). Thirteen (25%) had change of antibiotics because of deteriorating clinical state or drug resistance. Nine patients with unabated sepsis had bacteriological cultures which grew organisms resistant to the empirical antibiotics. Eight responded to the change of antibiotics. One patient with pseudomonas bacteraemia failed to respond to empirical treatment with ceftriaxone and died before antibiotics could be changed. Of the patients with positive cultures, the results of drug sensitivity made a difference to treatment. None of the patients with negative cultures died from sepsis. It appears that even though the rate of positive culture is low (27%), it is still useful as a guide when change of antibiotics is required.

Comparison of peripheral blood CD34+ concentration, colony-forming units granulocyte-macrophage and mononuclear cells in leukapheresed product for the prediction of peripheral blood CD34+ cell yield harvest.

The aim of this study was to evaluate reliability of parameters which may be used to guide peripheral stem cell harvests in cancer patients prior to myeloablative chemotherapy. Each leukapheresed product was analysed for CD34-positive (CD34+) cell count, mononuclear cell (MNC) count and the number of colony-forming units granulocyte-macrophage (CFU-GM). Each patient's peripheral blood (PB) taken before leukapheresis was analysed for CD34+ concentration. We evaluated whether the CD34+ yield from leukapheresis correlated with any of the three parameters. A total of 119 procedures were performed in 33 patients. The yield of CD34+ cells by leukapheresis correlated weakly but significantly with the peripheral blood CD34+ cell count (R = 0.4 P < 0.05), the MNC cells (R = 0.4, P < 0.05), and CFU-GM (R = 0.4, P < 0.05). When a PB CD34+ count of 50 x 10(6)/L was used as a cut-off value, the accuracy for prediction of adequate leukapheresis (> 1 x 10(6) CD34+ cells/kg) was 78%.

Gastrointestinal lymphoma--a review of 54 patients in Singapore.

Primary gastrointestinal (GI) lymphoma accounts for 2% to 5% of all GI malignancies. Primary therapy in uncomplicated GI lymphoma remains controversial. Fifty-four patients (male to female ratio of 4:3, median age 56 years) with GI lymphoma were studied to evaluate complications and results of therapy. The sites involved were the stomach (31), small bowel (12), large bowel (4), gallbladder (1) and multifocal (6). Distribution by stage and grade (Working Formulation or Kiel) were: IE-30%, IIE-43%, IIIE-6%, IV-20% and unknown-1%; low grade-33%, intermediate grade-59% and high grade-8%. Majority (54%) had diffuse large cell lymphoma. Twenty-three patients (43%) underwent primary resection of the tumour followed by chemotherapy in 14 or radiotherapy in 3. Seventeen patients (31%) had primary chemotherapy and 3 (6%) had primary radiotherapy. Of the 48 patients who underwent therapy, 52% had complete response. At the last follow-up (median 21 months), 25 patients were disease-free. Overall survival was 67% at two years. Treatment strategies employing surgery, radiotherapy and chemotherapy, alone or in combination, do not appear to influence outcome. Surgical resection plus chemotherapy appear to be effective in the control of local and distant disease.

5-Fluorouracil continuous infusion in metastatic colorectal cancer.

5-Fluorouracil (5-FU) remains the most active therapeutic agent in advanced colorectal cancer. This drug has demonstrated differing levels of activity dependent on the schedule of administration in experimental and clinical models. Twenty-six patients were treated with prolonged continuous infusion of 5-FU at 250 mg/m2/day via a portable infusion pump and Hickman's central venous catheter in this study. Twelve patients (46%) experienced a major response (complete response-1, partial response-11). Median duration of response was 5 months. Seventeen patients were chemotherapy-naive on accrual to this study. Ten patients from this group had partial responses (59%) and four were minor responders (24%). Hence 82% of patients who had no prior chemotherapy showed tumour responses to 5-FU continuous infusion. Two of nine patients (22%) with prior chemotherapy achieved major response. Favourable toxicity profile was noted with this regimen. Two patients discontinued therapy due to treatment-related toxicities (severe palmar-plantar erythrodysesthesia and superior vena cava thrombosis secondary to the central venous catheter). Prolonged continuous infusion of 5-FU could well be the standard treatment of advanced colorectal cancer in view of its favourable activity and toxicity profile. The serial serum carcino-embryonic antigen (CEA) trend was shown to correlate well to the objective response; a decline of more than 50% from baseline CEA level correlated with a major response and a rise of more than 50% correlated with progressive disease. Hence the use of serum CEA is suitable for monitoring response to chemotherapy which is advantageous with respect to patient convenience and cost-effectiveness.

A phase II trial of etoposide, leucovorin and 5-fluorouracil (ELF) in patients with advanced gastric cancer.

Etoposide, leucovorin and 5-fluorouracil (ELF) chemotherapy has been reported to be less toxic yet effective (response rates of 50%) in patients with advanced gastric cancer. A phase II study of ELF in 25 patients (11 males, 14 females, median age 53 years) with advanced adenocarcinoma of the stomach is reported. Patients received outpatient intravenous etoposide 120mg/m2 over 2 hours, folinic acid 300 mg/m2 over 2 hours, 5-fluorouracil 500 mg/m2 boluses daily for 3 days every 21 days. Of 17 measurable patients, there was one complete response (CR), 4 partial responses (PR) for a total response rate of 29.4%. Non-hematologic toxicity was modest (grade 0 vomiting 11/21, stomatitis 16/21, diarrhea 17/21). Grade 3/4 neutropenia was seen in 14/23, thrombocytopenia in 2/23, anemia in 5/23 patients. Median progression-free and overall survival was 4.1 and 7.1 months, respectively. In conclusion, ELF chemotherapy shows only modest activity in patients with advanced gastric cancer and is associated with severe hematologic toxicity.

Treatment of small cell lung cancer: a single institutional experience.

Forty-three patients with either limited or extensive small cell lung carcinoma were treated with either etoposide and cisplatin (EP) regimen or EP alternating with cyclophosphamide, doxorubicin and vincristine. Patients with limited disease were consolidated with radiotherapy. Responses were 96% (44% complete response) and 71% (6% complete response) in the patients with limited and extensive diseases, respectively. The 2-year disease-free and overall survival in the limited disease patients were 19% and 27%, respectively. None of the patients with extensive disease survived beyond 2 years. Toxicity of the therapy was acceptable. Forty percent developed grade 2 vomiting. Two patients had neutropenic fever of which one was fatal. One of the two-year survivors developed a second malignancy (oesophageal carcinoma). Despite consolidative radiotherapy in all responding patients with limited disease, 73% of the failure included a locoregional component. In the entire group, one-third of the patients developed brain metastases. Hence, more effective drugs and local treatment modalities are needed to improve this result.

Chemotherapy in non-small cell lung cancer: a review.

Lung cancer, of which non-small cell carcinoma is the most common, has been a significant therapeutic challenge for decades and will remain so for decades to come. Despite its prevalence, progress in the management of non-small cell lung cancer has been relatively slow. This is in part due to the pessimism of most physicians treating this disease, which has resulted in a relatively lackadaisical attitude with regards to clinical trials when compared to other solid tumours like breast or colorectal cancers. Nevertheless, the past decade has seen significant progress, specifically with regards to the management of locally advanced disease. Chemotherapy, though shown to be biologically active in non-small cell lung cancer, is considered an ineffective palliative tool in the setting of metastatic disease due to its toxicities and the "less than encouraging" response rates generated by the cisplatin-based combination regimen which is generally considered to be the most active currently available. The advent of new active agents such as paclitaxel and vinorelbine which are potentially less toxic may change this view. Conversely, the response rate of locally advanced disease to chemotherapy is significantly higher and this has resulted in numerous multimodality trials of neoadjuvant chemotherapy prior to surgery and/or radiation. To date, a number of randomised trials have shown that this approach can result in significant survival benefit for patients with locally advanced disease. An alternative approach makes use of the potential synergism between certain chemotherapeutic agents (such as cisplatin) and radiation when used concurrently. However, data on concurrent chemoradiotherapy in locally advanced disease have been largely based on single-arm studies and are inconclusive. Three randomised trials on concurrent chemoradiotherapy have been shown benefit for the use of combined modality in locally advanced disease. Hence, treatment of locally advanced disease should include chemotherapy as part of the combined modality approach. However, the optimal sequencing of these modalities would require well-designed randomised trials to determine.

Measuring quality of life in different cultures: translation of the Functional Living Index for Cancer (FLIC) into Chinese and Malay in Singapore.

Quality-of-life assessment has become an accepted method of evaluation in clinical medicine. The technique is based on a patient's self-assessment of physical, psychological, and social function, as well as the effects of distressing physical symptoms. The most important aspect of quality-of-life assessment is that it brings into focus a patient-centred view of health outcome, which is broader than the physiologic measures which predominate in Western medicine. Strategies for the development and use of assessment questionnaires have evolved over the past 15 years, and numerous questionnaires have been created. Most originate in Western societies, with English as the most common language of development. Adapting such questionnaires for use in other language and cultural settings is an imprecise practice. Language translation and equivalent cultural meaning must both be addressed. This paper reports on the language translation process and results for the Functional Living Index for Cancer (FLIC) as translated into Chinese and Malay in Singapore. We employed a step-wise process beginning with translation/back translation, followed by structured pilot field trials and population sampling. Taped versions of the questionnaire were devised to meet illiteracy problems in the sample population. Paired comparisons of the Chinese and Malay versions of individual questions with their English counterparts show good correlations and similar means most of the time. Factor analysis on a population sample of 246 (112 Chinese, 35 Malay and 98 English speaking) with cancers of minimal, extensive or palliative extent is convergent with that obtained on a North American population. However, a separate analysis of the Chinese questionnaires showed some differences in factor pattern. Specific language and cultural translation difficulties are discussed. Of note is the predicted significant decrease in total FLIC scores with extent of disease within each of the language preference populations, which provides some evidence for the validity for each language version in the Singapore culture(s). Thus, the FLIC translations into Malay and Chinese in Singapore can be considered for use in local trials, subject to ongoing evaluation.