A phase II study evaluating the safety and efficacy of an adenovirus-ΔLMP1-LMP2 transduced dendritic cell vaccine in patients with advanced metastatic nasopharyngeal carcinoma.

BACKGROUND: Individuals with metastatic Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) continue to have poor outcomes. To evaluate the ability of a dendritic cell (DC) vaccine to target subdominant EBV antigens LMP1 and LMP2 expressed by NPC cells, we vaccinated patients using autologous DCs transduced with an adenovirus encoding a truncated LMP1 (ΔLMP1) and full-length LMP2 (Ad-ΔLMP1-LMP2). MATERIALS AND METHODS: Sixteen subjects with metastatic NPC received Ad-ΔLMP1-LMP2 DC vaccines i.d. biweekly for up to five doses. Toxicity, immune responses and clinical responses were determined. RESULTS: Most patients had extensive disease, with a median of three visceral sites of involvement (range 1-7). No significant toxicity was observed. Ad-ΔLMP1-LMP2 DCs induced delayed type hypersensitivity responses in 9 out of 12 patients, but although these DCs activated LMP1/2-specific T cells in vitro, no such increase in the frequency of peripheral LMP1/2-specific T cells was detected. Three patients had clinical responses including one with partial response (for 7½ months) and two with stable disease (for 6½ and 7½ months). CONCLUSIONS: Ad-ΔLMP1-LMP2 transduced DCs can be successfully generated and safely administered to patients with advanced NPC. Since efficacy was limited, future studies should focus on DC vaccines with greater potency administered to subjects with less tumor burden.

Docetaxel is effective in heavily pretreated patients with disseminated nasopharyngeal carcinoma.

BACKGROUND: To evaluate the efficacy and toxicity of single-agent docetaxel (Taxotere) as therapy in patients with disseminated nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Patients with histologically confirmed metastatic or recurrent NPC who have failed at least one line of palliative chemotherapy regimen but no prior docetaxel were eligible. Patients received weekly docetaxel every 28 days (docetaxel 30 mg/m(2) on days 1, 8 and 15) and were evaluated every two cycles of treatment of response assessment. Quality-of-life (QoL) assessments during the treatment period were done using the European Organization for Research and Treatment of Cancer QoL questionnaire QLQ-C30; version 3.0. RESULTS: Thirty patients were assessable for toxicity and response. The median age of the patients was 47 years (range 25-68 years) and the majority of patients had good performance status (Eastern Cooperative Oncology Group 0-1). Grade 3 or 4 toxicity included fatigue (13%), anemia (10%) and diarrhea (3%) of patients. Eleven (37%) and four (13.3%) patients achieved partial response and stable disease, respectively. The median progression-free survival was 5.3 months and median overall survival of 12.8 months. The partial responders had a mean duration of response of 4.1 months. Docetaxel caused a significant decline in QoL scores during treatment of patients responding or progressing with the treatment. CONCLUSIONS: Our findings suggest that weekly docetaxel is well tolerated and is an active agent in patients with disseminated NPC who were previously exposed and largely refractory to platinum-based chemotherapy but can cause a significant decline in QoL during treatment.

Graft-vs-tumor effect in patients with advanced nasopharyngeal cancer treated with nonmyeloablative allogeneic PBSC transplantation.

While nonmyeloablative peripheral blood stem cell transplantation (NST) has shown efficacy against several solid tumors, it is untested in nasopharyngeal cancer (NPC). In a phase II clinical trial, 21 patients with pretreated metastatic NPC underwent NST with sibling PBSC allografts, using CY conditioning, thymic irradiation and in vivo T-cell depletion with thymoglobulin. Stable lymphohematopoietic chimerism was achieved in most patients and prophylactic CYA was tapered at a median of day +30. Seven patients (33%) showed partial response and three (14%) achieved stable disease. Four patients were alive at 2 years and three showed prolonged disease control of 344, 525 and 550 days. With a median follow-up of 209 (4-1147) days, the median PFS was 100 days (95% confidence interval (CI), 66-128 days), and median OS was 209 days (95% CI, 128-236 days). Patients with chronic GVHD had better survival-median OS 426 days (95% CI, 194-NE days) vs 143 days (95% CI, 114-226 days) (P=0.010). Thus, NST may induce meaningful clinical responses in patients with advanced NPC.

Phase I pharmacokinetic study of a weekly liposomal paclitaxel formulation (Genexol-PM) in patients with solid tumors.

BACKGROUND: The aim of this study was to determine the maximum tolerated dose (MTD) and the pharmacokinetic profile of Genexol-PM in Asian cancer patients. MATERIALS AND METHODS: Patients (N = 24) refractory to previous chemotherapy received Genexol-PM as an 1-h infusion on a weekly basis for 3 weeks followed by a resting week. The starting dose was 80 mg/m(2) and the maximum administered dose was 200 mg/m(2). RESULTS: The majority of patients had lung, nasopharyngeal and breast cancers and in eleven patients (46%), taxane-based chemotherapy had previously failed. The MTD was defined at 180 mg/m(2). The most common grade 3 non-hematologic adverse events in cycle 1 were fatigue (4%) and neuropathy (4%) occurring mainly at 200 mg/m(2). Five (21%) patients had partial response, nine (38%) had stable disease and seven (29%) had disease progression. Five of 11 previously taxane-refractory patients showed clinical benefit to Genexol-PM. The pharmacokinetics of Genexol-PM displayed dose-proportionality, with both the maximum concentration (C(max)) and the area under the concentration-time curve from zero to infinity (AUC(0-infinity)) increasing by approximately four- and threefold, respectively, as the dose of Genexol-PM was escalated from 80 to 200 mg/m(2). The median total-body clearance of Genexol-PM for all patients was 43.9 l/h. CONCLUSION: The weekly regimen of Genexol-PM was well tolerated and responses were observed in patients with refractory tumors, including patients who had failed taxane-based chemotherapy previously.

Phase II trial of gemcitabine and cisplatin sequentially administered in Asian patients with unresectable or metastatic non-small cell lung cancer.

INTRODUCTION: The aim of this study was to assess toxicity and response in the sequential administration of gemcitabine followed by cisplatin in unresectable or metastatic non-small cell lung cancer. MATERIALS AND METHODS: Twenty-three patients were enrolled in this study. Gemcitabine was given at 1,250 mg/m2 on days 1 and 8, for four 21-day cycles. RESULTS: There were 4 patients with partial responses. 5 patients with stable disease and 10 patients with progressive disease, giving a response rate of 21%. The median time to disease progression was 3.3 months. The median overall survival was 14.6 months. Toxicities graded 3 or 4 included anaemia (13.0%), neutropaenia (13.0%), supraventricular tachycardia (4.3%), and nausea and vomiting (4.3%). CONCLUSION: Although these results show similar efficacy to single-agent treatment regimens, the low toxicity profile and promising survival outcome with this regimen are important points for consideration.

Concurrent chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the oesophagus: a single centre experience.

INTRODUCTION: Data on combined modality treatment for locally advanced squamous cell carcinoma of the oesophagus involving Asian patients are limited. MATERIALS AND METHODS: A retrospective study of 56 consecutive patients with this condition treated with concurrent chemoradiotherapy followed by surgery in a single tertiary institution in Singapore was performed. RESULTS: The median overall survival of the entire cohort was 14.1 months [95% confidence interval (CI); range, 8.6 to 19.6 months]. In patients who underwent successful oesophagectomy after chemoradiotherapy (n = 17), the median survival was 27.8 months compared to 9.8 months for those who did not have surgery (n = 39) (P = 0.046, log-rank test). The median time to first relapse for the entire cohort was 16.1 months (95% CI, 7.7 to 24.5 months). The time to first relapse was 23.9 months in the subgroup of patients with successful surgery and 12.1 months in the group which did not (P = 0.147, log-rank test). The high proportion of patients who were medically unfit for surgery or declined surgery may have conferred a selection bias. CONCLUSION: Concurrent chemoradiotherapy followed by surgery is feasible in selected patients. The benefit of adding of surgery to chemoradiotherapy is still controversial and we await the results of randomised controlled trials comparing chemoradiotherapy with surgery versus chemoradiotherapy alone.

Surgery and adjuvant radiotherapy vs concurrent chemoradiotherapy in stage III/IV nonmetastatic squamous cell head and neck cancer: a randomised comparison.

We compared concurrent combination chemotherapy and radiotherapy with surgery and adjuvant radiotherapy in patients with stage III/IV nonmetastatic squamous cell head and neck cancer. Patients with non-nasopharyngeal and nonsalivary resectable squamous cell head and neck cancer were randomised to receive either surgery followed by adjuvant radiotherapy (60 Gy over 30 fractions) or concurrent combination chemotherapy and radiotherapy (66 Gy in 33 fractions). Combination chemotherapy comprised two cycles of i.v. cisplatin 20 mg m(-2) day(-1) and i.v. 5-fluorouracil 1000 mg m(-2) day(-1), both to run over 96 h given on days 1 and 28 of the radiotherapy. A total of 119 patients were randomised. At a median follow-up of 6 years, there was no significant difference in the 3-year disease-free survival rate between the surgery and concurrent chemoradiotherapy (50 vs 40% respectively). The overall organ preservation rate or avoidance of surgery to primary site was 45%. Those with laryngeal/hypopharyngeal disease subsite had a higher organ-preservation rate than the rest (68 vs 30%). Combination chemotherapy and concurrent irradiation with salvage surgery was not superior to conventional surgery and postoperative radiotherapy for resectable advanced squamous cell head and neck cancer. However, this form of treatment schedule with a view to organ-preservation can be attempted especially for those with laryngeal/hypopharyngeal and possibly oropharyngeal disease subsites.

Gefitinib is more effective in never-smokers with non-small-cell lung cancer: experience among Asian patients.

We retrospectively analysed the results of patients with advanced non-small-cell lung cancer treated with gefitinib to derive clinical factors predictive of response and a favourable survival outcome. Patients were treated with gefitinib 250 mg per day and re-evaluated 4-8 weeks later with repeat CT scan and every 8 weeks thereafter to assess response and the duration of response. Pathology review by a histopathologist was conducted, in particular to confirm a recently published result of bronchioloalveolar carcinoma histology or its components as predictive of response to gefitinib. Logistic regression and Cox regression analytical methods were applied to determine factors that could predict for response and improved overall survival. A total of 110 patients were treated. The overall response rate was 32% partial responses (PRs). Only never-smoking status was predictive of response in the logistic regression analysis, adjusted OR=6.1, 95% CI=1.7, 21.5. The presence of a PR and good performance status were predictive of a favourable survival outcome from the Cox regression modelling. Responders had an adjusted HR of 3.0, 95% CI=1.5-5.8 compared to nonresponders, while patients with ECOG status 0-1 had an adjusted HR of 0.42, 95% CI=0.25-0.72, compared with patients with ECOG status 2-4. Bronchioloalveolar carcinoma or its components were distinctly absent on pathology review. In conclusions, Never-smoking status is an important clinical predictor of a favourable response to gefitinib.

Validation of a new prognostic index score for disseminated nasopharyngeal carcinoma.

Patients with metastatic nasopharyngeal carcinoma have variable survival outcomes. We previously designed a scoring system to better prognosticate these patients. Here, we report results on validation of this new prognostic index score in a separate cohort of patients. Clinical features and laboratory parameters were examined in 172 patients with univariate and multivariate analyses and a numerical score was derived for each independent prognostic variable. Significant independent prognostic variables and their scores assigned included poor performance status (score 5), haemoglobin < 12 g dl(-1) (score 4) and disease-free interval (DFI) (DFI < or = 6 months (score 10) or metastases at initial diagnosis (score 1)). Maximum score was 19 and patients stratified into three prognostic groups: good, 0-3; intermediate, 4-8; poor, > or = 9. When applied to a separate cohort of 120 patients, 59 patients were good, 43 intermediate and 18 poor prognosis, with median survivals of 19.6 (95% CI 16.1, 23.1), 14.3 (95% CI 12.3, 16.2) and 7.9 (95% CI 6.6, 9.2) months, respectively. (logrank test: P = 0.003). We have validated a new prognostic score with factors readily available in the clinics. This simple score will prove useful as a method to prognosticate and stratify patients as well as to promote consistent reporting among clinical trials.

A case of metastatic squamous cell carcinoma of the hypopharynx manifesting as acute abdomen.

INTRODUCTION: Squamous cell head and neck cancers are usually confined to local and regional sites but occasionally, patients may present with rare manifestations of distant metastases. CLINICAL PICTURE: A 23-year-old female was treated with concurrent chemo-radiotherapy for stage IVA post-cricoid squamous cell carcinoma. A month later, she presented with acute abdomen and was found to have extensive peritoneal nodules at laparotomy. Intestinal obstruction soon followed. TREATMENT: She was managed conservatively for the intestinal obstruction and given weekly paclitaxel. OUTCOME: She continued to deteriorate and succumbed shortly after the diagnosis of carcinomatosis peritoneii. CONCLUSION: This rare and aggressive presentation reminds us to be cognizant of relapsed head and neck cancers manifesting atypically, and the need for more aggressive search of distant disease in at least some subgroups of head and neck cancer.

Quick-FLIC: validation of a short questionnaire for assessing quality of life of cancer patients.

A practically useful measure of quality of life should be simple and quick to complete. A shortened Chinese version of the Functional Living Index - Cancer (FLIC) was recently proposed and was called Quick-FLIC. This study aims to assess the measurement properties of the Quick-FLIC. A total of 190 patients who received care from the National Cancer Centre of Singapore completed a questionnaire package at baseline. Patients filled in a retest questionnaire on average 2 weeks after baseline to assess test-retest reliability and responsiveness to change. The Quick-FLIC scores correlated well with the Functional Assessment of Chronic Therapy - General scores (r=0.78). Patients with different treatment status, performance status and self-rated health had significantly different Quick-FLIC scores in the expected directions (ANOVA; each P<0.001). Internal consistency (Cronbach's alpha=0.87) and 2-week test-retest reliability (intraclass correlation=0.81) were also satisfactory. The measure was responsive to changes in health status (P<0.001). The Quick-FLIC is a valid and reliable measure of health-related quality of life of cancer patients. The shortening of established health-related quality of life instruments should be considered in order to reduce the burden of having patients to answer lengthy questionnaires.

A multicenter phase II study of the efficacy and safety of docetaxel plus cisplatin in Asian chemonaïve patients with metastatic or locally advanced non-small cell lung cancer.

AIMS: To evaluate the efficacy and safety of docetaxel-cisplatin in patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). METHODS: Chemotherapy-naïve patients with histologically confirmed TNM stage III or IV NSCLC were recruited from 12 Asian trial centers. Patients received docetaxel (75 mg/m2) and cisplatin (75 mg/m2) every 3 weeks for 6 cycles. RESULTS: 130 of 146 patients were evaluable for efficacy (60% stage IV). Three complete and 58 partial responses were observed (overall response rate: 46.9%; 95% CI: 38.3-55.5%). Median time to progression was 6.9 months and median survival was 14.0 months; 1-year survival was 59.5%. Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 69.2%, 6.2% and 18.5% of patients, respectively. Grade 3/4 vomiting was observed in 13.7% and grade 3/4 neurosensory effects were observed in 2.7% of patients. There was one case of treatment-related death due to sepsis. CONCLUSION: Docetaxel-cisplatin is an effective and well-tolerated treatment in Asian patients with NSCLC.

Design of a prognostic index score for metastatic nasopharyngeal carcinoma.

The survival outcome of patients with systemic cancer differs significantly between individuals even within the same tumour type. We set out to illustrate this by analysing the factors determining survival in patients with metastatic disease from nasopharyngeal carcinoma (NPC) and to design a scoring system based on these prognostic factors. Patients referred between January 1994 and December 1999 were retrospectively analysed. Factors analysed included patient (age group, gender, performance status (BS) at diagnosis of metastases), disease (number of metastatic sites, specific metastatic sites, disease-free interval (DFI), metastases at presentation, presence of locoregional recurrence), and laboratory factors (leucocyte count, haemoglobin level, albumin level). Univariate and multivariable analyses were performed using the Cox proportion hazards model. A numerical score was derived from the regression coefficients of each independent prognostic variable. The prognostic index score (PIS) of each patient was calculated by totalling up the scores of each independent variable. Independently significant, negative prognostic factors were liver metastasis, lung metastasis, anaemia, poor PS, distant metastasis at initial diagnosis, and a DFI of <6 months. Three prognostic groups based on the PIS were obtained: (i) good risk (PIS=0-6); (ii) intermediate risk (7-10); (iii) poor risk (>or=11). The median survivals for these groups were 19.5, 10, and 5.8, months, respectively, (log rank test: P<0.0001). The variable prognosis of patients with disseminated NPC can be assessed by using easily available clinical information (patient, disease and laboratory factors). The PIS system will need to be validated on prospectively collected data of another cohort of patients.

Gemcitabine in metastatic nasopharyngeal carcinoma of the undifferentiated type.

BACKGROUND: We conducted two parallel phase II trials in chemonaïve and previously treated patients with metastatic nasopharyngeal carcinoma (NPC) to evaluate the tumour response, progression-free and overall survival, and toxicity of gemcitabine. PATIENTS AND METHODS: Gemcitabine 1250 mg/m2 was given on days 1 and 8 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status <2, adequate renal, hepatic and bone marrow function, and radiologically measurable NPC were eligible. RESULTS: Twenty-five chemonaïve and 27 previously treated patients were enrolled. The overall response rate was 28% [95% confidence interval (CI) 14% to 48%] for the chemonaïve and 48% (95% CI 31% to 66%) for previously treated patients. Toxicities greater than or equal to grade 3 occurred in 15 (60%) chemonaïve and 13 (48%) previously treated patients. Neutropenia was uncommon in chemonaïve patients, but occurred in 37% of previously treated patients. The median time to progression was 3.6 months (range 0.9-7.9) for chemonaïve and 5.1 months (0.9-13.1) for previously treated patients. Median overall survival time was 7.2 months (1.4-15.6) and 10.5 months (2.4-15.0) for chemonaïve and previously treated patients, respectively. CONCLUSIONS: Gemcitabine has moderate activity in NPC with minimal toxicity, and is also an effective salvage agent for patients who have failed or progressed after treatment with other agents.

Primary intrathoracic malignant effusion: a descriptive study.

BACKGROUND: Patients who present with malignant pleural/malignant effusion without a definite primary site are not well described in the medical literature. In the course of our clinical practice, we have observed certain traits that are peculiar to patients with such a presentation. We have applied the term primary intrathoracic malignant effusion (PIME) to describe this condition. STUDY OBJECTIVES: Patients must fulfill the following criteria before a diagnosis of PIME can be made: clinical presentation dominated by pleural/pericardial effusion; histologic proof of malignancy obtained from the pleura and/or pericardium; no definite primary site in the lungs or elsewhere from CT scan of the chest, chest radiograph, or physical and endoscopic examination; no history of malignancy; and no history of asbestos exposure. Exposure to environmental tobacco smoke (ETS) among the nonsmokers was examined in a case-control setting. METHODS: We conducted a retrospective search of our database of patients who were referred to the Department of Medical Oncology with a diagnosis of pleural/pericardial effusion from January 1993 to January 2000. RESULTS: Seventy-one of 200 patients from our database met the criteria. A significant majority of the patients were women (65%) and nonsmokers (72%). All patients had adenocarcinoma shown on biopsy. The majority of patients (63%) had disease localized to the intrathoracic serosal surfaces; the rest had distant metastases involving the lung (50%), bone (27%), liver (19%), brain (8%), and skin (4%). Six patients had two or more sites of distant metastases. There was a significant association with ETS exposure when compared to a control group comprised of patients with colonic cancer, matched for sex and age. The median survival was 10 months for patients with disease localized to the pleura/pericardium and 7 months for those with distant metastases. Thirty-eight patients (54%) received chemotherapy. All had platinum-based chemotherapy, except for three patients. The median survival for patients treated or not treated with chemotherapy was 12 months and 5 months, respectively. This difference in survival was statistically significant (p = 0.003). CONCLUSIONS: PIME should be viewed as a distinct entity. Its etiology remains largely unknown, although exposure to environmental tobacco smoke may play a part. Platinum-based chemotherapy may have a positive biological effect on this disease. More studies are required to elucidate the epidemiology, possible etiologic factors, and treatment options for this group of patients.

Recurrent nasopharyngeal carcinoma presenting as diffuse dermal lymphatic infiltration in the neck: three case reports.

BACKGROUND: Any malignancy has the propensity to metastasize to skin. The frequency of skin metastases vary in different tumors and occur in about 0.7% to 10% of all patients diagnosed with cancer. It is rare in nasopharyngeal carcinoma. METHOD: Three cases of relapsed nasopharyngeal carcinoma with diffuse dermal involvement were described. Their clinical presentation, results of investigations, and response to treatment were reviewed. Literature review of similar forms of presentation was done by means of a MEDLINE search. RESULTS: At the time of dermal relapse, all three patients had a uniform clinical picture of facial, periorbital, and lip swelling associated with stridor and dysphagia. Histologic findings showed dermal infiltrates of malignant cells, and CT scan showed diffuse infiltration of the subcutaneous tissue. Despite chemotherapy, the clinical course was relentless. CONCLUSION: This report describes a presentation of disease that is underdiagnosed and heightens awareness of oncologists to this form of recurrence in nasopharyngeal carcinoma.

Single-agent gemcitabine and gemcitabine/irinotecan combination (irimogem) in non-small cell lung cancer.

Gemcitabine is a fluoridated pyrimidine related to cytosine arabinoside that has significant activity in solid tumor models. Irinotecan is a camptothecin analog with an active metabolite, SN-38, which inhibits topoisomerase I activity by stabilizing the topoisomerase I-DNA cleavable complex. Gemcitabine studies in non-small cell lung cancer conducted in the United States, as well as an international collaboration and clinical trials from Europe and Japan, found overall response rates of 20% to 26%, a median duration of response between 5 to 9 months, and a median duration of survival ranging from 7 to 12.3 months. Gemcitabine also has been shown to be more effective than best supportive care in non-small cell lung cancer. In a phase I trial of irinotecan (50, 75, 100, and 115 mg/m2) in combination with 1,000 mg/m2 gemcitabine, three patients had documented partial responses: one with pancreas cancer at irinotecan 100 mg/m2, one with pancreas cancer, and one with metastatic carcinoma of unknown primary at irinotecan 115 mg/m2. Three of five non-small cell lung cancer patients had stable disease for four or more cycles at irinotecan doses of 50, 75, and 100 mg/m2; no non-small cell lung cancer patients were treated at irinotecan 115 mg/m2. We recommend that a combination of gemcitabine 1,000 mg/m2 and irinotecan 100 mg/m2 given on days 1 and 8 every 3 weeks be used as the starting dose in future phase II studies. Furthermore, based on the absence of severe nonhematologic toxicity or grade IV hematologic toxicity in the majority of patients treated at the highest dose, escalation of irinotecan to 115 mg/m2 may be considered for subsequent cycles in patients who do not experience > or =grade I hematologic or non-hematologic toxicity during the first cycle of gemcitabine/irinotecan combination chemotherapy.

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.

The 1997 International Staging System for non-small cell lung cancer: have all the issues been addressed?

The International Staging System for Lung Cancer has been revised recently. Important changes have been made to allow better correlation of prognoses and direction of management. The classification of synchronous pulmonary nodules in the same lobe as the primary tumor as T4 stage IIIB may imply a poorer outcome than is warranted, while the designation of a similar stage for malignant pleural effusion may not be reflective of the very poor prognosis associated with this extent of disease.