Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer (GC), published in late 2022 and the updated ESMO Gastric Cancer Living Guideline published in July 2023, were adapted in August 2023, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with GC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with GC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), coordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with GC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer (mCRC), published in late 2022, were adapted in December 2022, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with mCRC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with mCRC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian countries. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with mCRC across the different countries of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation, coupled with a disparity in the drug approvals and reimbursement strategies, between the different countries.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of localised colon cancer was published in 2020. It was decided by both the ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special virtual guidelines meeting in March 2021 to adapt the ESMO 2020 guidelines to take into account the ethnic differences associated with the treatment of localised colon cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with localised colon cancer representing the oncological societies of Japan (JSMO), China (CSCO), India (ISMPO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug availability and reimbursement situations in the different Asian countries.

JSCO-ESMO-ASCO-JSMO-TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions.

A Japan Society of Clinical Oncology (JSCO)-hosted expert meeting was held in Japan on 27 October 2019, which comprised experts from the JSCO, the Japanese Society of Medical Oncology (JSMO), the European Society for Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), and the Taiwan Oncology Society (TOS). The purpose of the meeting was to focus on what we have learnt from both microsatellite instability (MSI)/deficient mismatch repair (dMMR) biomarkers in predicting the efficacy of anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) immunotherapy, and the neurotrophic tyrosine receptor kinase (NTRK) gene fusions in predicting the efficacy of inhibitors of the tropomyosin receptor kinase (TRK) proteins across a range of solid tumour types. The recent regulatory approvals of the anti-PD-1 antibody pembrolizumab and the TRK inhibitors larotrectinib and entrectinib, based on specific tumour biomarkers rather than specific tumour type, have heralded a paradigm shift in cancer treatment approaches. The purpose of the meeting was to develop international expert consensus recommendations on the use of such tumour-agnostic treatments in patients with solid tumours. The aim was to generate a reference document for clinical practice, for pharmaceutical companies in the design of clinical trials, for ethics committees in the approval of clinical trial protocols and for regulatory authorities in relation to drug approvals, with a particular emphasis on diagnostic testing and patient selection.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic oesophageal cancer: a JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of oesophageal cancer was published in 2016, and covered the management and treatment of local/locoregional disease, limited disease, locally advanced disease and the management of advanced/metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic oesophageal cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic oesophageal cancer representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic gastric cancer: a JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of gastric cancer (GC) was published in 2016, and covered the management and treatment of local, locoregional, locally advanced and metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and The Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic GC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic GC representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.

Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: a JSMO-ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS.

The most recent version of the European Society for Medical Oncology (ESMO) consensus guidelines for the treatment of patients with metastatic colorectal cancer (mCRC) was published in 2016, identifying both a more strategic approach to the administration of the available systemic therapy choices, and a greater emphasis on the use of ablative techniques, including surgery. At the 2016 ESMO Asia Meeting, in December 2016, it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting, endorsed by both ESMO and JSMO, immediately after the JSMO 2017 Annual Meeting. The aim was to adapt the ESMO consensus guidelines to take into account the ethnic differences relating to the toxicity as well as other aspects of certain systemic treatments in patients of Asian ethnicity. These guidelines represent the consensus opinions reached by experts in the treatment of patients with mCRC identified by the Presidents of the oncological societies of Japan (JSMO), China (Chinese Society of Clinical Oncology), Korea (Korean Association for Clinical Oncology), Malaysia (Malaysian Oncological Society), Singapore (Singapore Society of Oncology) and Taiwan (Taiwan Oncology Society). The voting was based on scientific evidence and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.

Phase I study of nanoliposomal irinotecan (PEP02) in advanced solid tumor patients.

PURPOSE: To define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and pharmacokinetics (PK) of PEP02, a novel liposome-encapsulated irinotecan, in patients with advanced refractory solid tumors. METHODS: Patients were enrolled in cohorts of one to three to receive escalating dose of PEP02 in a phase I trial. PEP02, from 60 to 180 mg/m(2), was given as a 90-min intravenous infusion, every 3 weeks. RESULTS: A total of 11 patients were enrolled into three dose levels: 60 (one patient), 120 (six patients) and 180 mg/m(2) (four patients). DLT was observed in three patients, one at 120 mg/m(2) (grade 3 catheter-related infection) and two at 180 mg/m(2) (grade 4 neutropenia lasting for >3 days in one, grade 4 hematological toxicities and grade 4 diarrhea in the other). MTD was determined as 120 mg/m(2). Comparing with those after free-form irinotecan in the literature, the dose-normalized PK of SN-38 (the active metabolite) after PEP02 was characterized by lower C max, prolonged terminal half-life and higher AUC but with significant inter-individual variation. One patient who died of treatment-related toxicity had significantly higher C max and AUC levels of SN-38 than those of the other three patients at 180 mg/m(2). Post hoc pharmacogenetic study showed that the patient had a combined heterozygosity genotype of UGT1A1*6/*28. Two patients had objective tumor response. CONCLUSIONS: PEP02 apparently modified the PK parameters of irinotecan and SN-38 by liposome encapsulation. The MTD of PEP02 monotherapy at 3-week interval is 120 mg/m(2), which will be the recommended dose for future studies.

Helicobacter pylori-related diffuse large B-cell lymphoma of the stomach: a distinct entity with lower aggressiveness and higher chemosensitivity.

We recently showed that Helicobacter pylori (HP)-positive gastric 'pure' diffuse large B-cell lymphoma (DLBCL) may respond to HP eradication therapy. However, whether these HP-related 'pure' DLBCL of the stomach may differ fundamentally from those unrelated to HP remains unclear. In this study, we compared the clinicopathologic features of these two groups of patients who had been uniformly treated by conventional chemotherapy. Forty-six patients were designated HP-positive and 49 were HP-negative by conventional criteria. HP-positive patients had a lower International Prognostic Index score (0-1, 65% vs 43%, P=0.029), a lower clinical stage (I-IIE1, 70% vs 39%, P=0.003), a better tumor response to chemotherapy (complete pathologic response, 76% vs 47%, P=0.004) and significantly superior 5-year event-free survival (EFS) (71.7% vs 31.8%, P<0.001) and overall survival (OS) (76.1% vs 39.8%, P<0.001). To draw a closer biologic link with HP, HP-positive tumors were further examined for CagA expression in lymphoma cells. Compared with CagA-negative cases (n=16), CagA-positive cases (n=27) were associated with high phosphorylated SHP-2 expression (P=0.016), and even better 5-year EFS (85.2% vs 46.3%, P=0.002) and OS (88.9% vs 52.9%, P=0.003). HP-related gastric 'pure' DLBCL may be a distinct tumor entity, which is less aggressive, and responds better to conventional chemotherapy.

A phase I study of two dosing schedules of volasertib (BI 6727), an intravenous polo-like kinase inhibitor, in patients with advanced solid malignancies.

BACKGROUND: Polo-like kinase 1 (Plk1) has an important role in mitosis. Volasertib (BI 6727), a potent and selective cell cycle kinase inhibitor, induces mitotic arrest and apoptosis by targeting Plk; this phase I study sought to determine its maximum tolerated dose (MTD) in Asian patients with advanced solid tumours. METHODS: Patients were enrolled simultaneously into two 3-week schedules of volasertib: a 2-h infusion on day 1 (schedule A) or days 1 and 8 (schedule B). Dose escalation followed a 3+3 design. The MTD was determined based on dose-limiting toxicities (DLT) in the first treatment course. RESULTS: Among 59 treated patients, the most common first course DLTs were reversible thrombocytopenia, neutropenia and febrile neutropenia; MTDs were 300 mg for schedule A and 150 mg for schedule B. Volasertib exhibited multi-exponential pharmacokinetics (PK), a long terminal half-life of ∼135 h, a large volume of distribution (>3000 l), and a moderate clearance. Partial responses were observed in two pre-treated patients (ureteral cancer; melanoma). Volasertib was generally well tolerated, with an adverse event profile consistent with its antimitotic mode of action and a favourable PK profile. CONCLUSIONS: These data support further development of volasertib and a harmonised dosing for Asian and Caucasian patients.

High-dose tamoxifen plus ifosfamide and anthracycline in a patient with angiosarcoma of the breast / Tamoxifen en dosis alta con ifosfamida y antraciclina en un paciente con angiosarcoma de mama

Although breast cancer is, unfortunately, not uncommon in women, a mere 0.04% of malignant breast tumours are primary angiosarcomas. Chemotherapy is advocated for treatment of breast angiosarcomas; however, no guidelines exist regarding optimal chemotherapeutics or protocols. Presently, the prognosis for breast angiosarcomas is poor. This case report describes a 24-year old woman diagnosed with primary breast angiosarcoma. She initially refused to receive treatment, but later returned to the hospital four years later with a haemopneumothorax. She was treated with rescue chemotherapy using a combination of high-dose tamoxifen plus ifosfamide and epirubicin (an anthracycline). She achieved a partial response, but died 16 months after therapy was initiated. More research is needed to devise novel chemotherapeutics and protocols to improve outcomes in women diagnosed with primary angiosarcomas ofthe breast.

Aunque el cáncer de mama, desafortunadamente, no es poco común en las mujeres, apenas 0.04% de los tumores malignos de mama son angiosarcomas primarios. La quimioterapia es el tratamiento de preferencia en los casos de angiosarcomas de mama. Sin embargo, no existen guías en relación con los protocolos o la quimioterapia óptima. En la actualidad, el pronóstico para los angiosarcomas de mama es pobre. Este informe del caso describe a una mujer de 24 años diagnosticada con angiosarcoma primario de mama. Inicialmente la paciente se negó a recibir tratamiento, pero volvió al hospital cuatro años más tarde con un hemoneumotórax. Fue tratada entonces con quimioterapia de rescate usando una combinación de alta dosis de tamoxifen con ifosfamida y epirrubicina (antraciclina). Llegó a responder parcialmente al tratamiento, pero falleció 16 meses después del inicio de la terapia. Se necesitan más investigaciones para elaborar nuevos quimioterápeuticos y protocolos que mejoren los resultados en los casos de mujeres diagnosticadas con angiosarcomas primarios de mama.

Detection of the Helicobacter pylori CagA protein in gastric mucosa-associated lymphoid tissue lymphoma cells: clinical and biological significance.

We previously reported that CagA can be translocated into B cells in Helicobacter pylori (HP) coculture media, and the translocation appears biologically significant as activation of the relevant cellular pathways was noticed. In this study, we further explore if CagA can be detected in malignant B cells of HP-positive gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Expression of CagA was evaluated by immunohistochemistry. CagA expression was further confirmed by western blot analysis. The association between CagA expression in malignant B cells and tumor response to HP eradication therapy (HPE) was evaluated in 64 stage IE gastric MALT lymphoma patients. We detected CagA expression in 31 (48.4%) of 64 patients: 26 (68.4%) of the 38 HP-dependent cases and 5 (19.2%) of the 26 HP-independent cases (P<0.001). Patients with CagA expression responded to HPE quicker than those without (median time to complete remission, 3.0 vs 6.5 months, P=0.025). Our results indicated that CagA can be translocated into malignant B cells of MALT lymphoma, and the translocation is clinically and biologically significant.

Predictors of bloodstream infection associated with permanently implantable venous port in solid cancer patients.

BACKGROUND: The purpose of this study is to characterize the risk factors of bloodstream infection (BSI) associated with the use of permanent implantable venous ports (Port-A) in solid cancer patients. METHODS: Solid cancer patients implanted with a Port-A were prospectively observed for the occurrence of Port-A-associated BSI (PABSI), defined as BSI without other identifiable infection foci. A PABSI risk score was developed using the Cox proportional hazards model. RESULTS: A total of 415 patients were registered; 88 PABSI episodes occurred in 58 patients (incidence1.05 per 1000 catheter-days). All but one patient had stage IV cancer. Independent predictors of PABSI occurrence included neutropenia, total parenteral nutrition (TPN), chronic steroid use, invasive procedures, postoperative antibiotics, and preoperative antibiotics. A PABSI risk score with a cut-off value of 0 (sensitivity 88.5%, specificity 64.3%) was defined for stage IV cancer patients as follows: neutropenia, +1.350; TPN, +1.256; chronic steroid use, +1.947; preoperative antibiotics, -0.970; postoperative antibiotics, +0.959; and invasive procedures, +1.098. The median PABSI-free survival was 4.47 months for patients with scores ≥ 0 but not reached for patients with scores <0 (P < 0.0001). CONCLUSION: The PABSI risk score can assist in identifying high-risk solid cancer patients and may assist in designing future preventive strategies.

High-dose tamoxifen plus ifosfamide and anthracycline in a patient with angiosarcoma of the breast.

Although breast cancer is, unfortunately, not uncommon in women, a mere 0.04% of malignant breast tumours are primary angiosarcomas. Chemotherapy is advocated for treatment of breast angiosarcomas; however, no guidelines exist regarding optimal chemotherapeutics or protocols. Presently, the prognosis for breast angiosarcomas is poor. This case report describes a 24-year old woman diagnosed with primary breast angiosarcoma. She initially refused to receive treatment, but later returned to the hospital four years later with a haemopneumothorax. She was treated with rescue chemotherapy using a combination of high-dose tamoxifen plus ifosfamide and epirubicin (an anthracycline). She achieved a partial response, but died 16 months after therapy was initiated. More research is needed to devise novel chemotherapeutics and protocols to improve outcomes in women diagnosed with primary angiosarcomas of the breast.

Concurrent chemoradiotherapy with twice weekly paclitaxel and cisplatin followed by esophagectomy for locally advanced esophageal cancer.

BACKGROUND: To test the feasibility of incorporating a twice-weekly paclitaxel (Taxol) and cisplatin regimen into concurrent chemoradiotherapy (CCRT), followed by surgery, for patients with locally advanced esophageal cancer. PATIENTS AND METHODS: Patients with operable T3N0-1M0 or T1-3N1M0 esophageal cancer were enrolled. The CCRT regimen included paclitaxel (35 mg/m2 1 h on days 1 and 4/week), cisplatin (15 mg/m2 1 h on days 2 and 5/week), and radiotherapy (2 Gy on days 1-5/week). When the accumulated radiation dose reached 40 Gy, the feasibility of esophagectomy was evaluated in all patients. In patients for whom esophagectomy was not feasible, CCRT was continued to a dose of 60 Gy. RESULTS: The majority of 97 patients enrolled had squamous cell carcinoma on histology (95%) and T3N1 disease by endoscopic ultrasonographic staging (90%). All patients received CCRT to 40 Gy. Sixty-one patients underwent surgery, and 26 patients continued definitive CCRT to 60 Gy. The intention-to-treat pathological complete response rate was 25% [24/97, 95% confidence interval (CI) 16-33]. At a median follow-up of 25.3 months, the median progression-free and overall survival was 15.6 and 28.8 months, respectively. The most common grade 3/4 toxic effects were leukopenia (30%), thrombocytopenia (10%), and diarrhea (15%). CONCLUSIONS: CCRT with a twice-weekly paclitaxel and cisplatin regimen followed by esophagectomy is an active treatment of locally advanced esophageal cancer.

Differential response to H. pylori eradication therapy of co-existing diffuse large B-cell lymphoma and MALT lymphoma of stomach-significance of tumour cell clonality and BCL10 expression.

We recently reported that low-grade mucosa-associated lymphoid tissue lymphoma (MALToma) and diffuse large B-cell lymphoma (DLBCL) with MALToma (DLBCL[MALT]) of stomach are equally responsive to H. pylori eradication therapy (HPET) and that H. pylori-independent status is closely associated with nuclear translocation of BCL10. However, co-existing MALToma and DLBCL components of gastric DLBCL(MALT) may respond differentially to HPET and the underlying mechanism remains unclear. Tumour tissue samples from 18 patients with microdissectable co-existing MALToma and DLBCL cells were studied. The clonality of lymphoma cells was examined by polymerase chain reaction-based amplification of the CDR3 region of the IgH gene and confirmed by DNA sequence analysis. BCL10 expression was determined by immunohistochemistry. Differential response of co-existing MALToma and DLBCL to HPET was defined as complete eradication of one component while the other component remained. Five (27.8%) of the 18 patients showed different IgH gene rearrangements in the two components and three (60%) of these five patients had differential response of MALToma and DLBCL to HPET. By contrast, 13 patients showed identical IgH gene rearrangements and only one (8%) of them had differential response of the two components to HPET (p = 0.044). Further, all four patients with differential response of MALToma and DLBCL to HPET showed nuclear expression of BCL10 in the H. pylori-independent component and cytoplasmic expression of BCL10 in the H. pylori-dependent component while the expression patterns of BCL10 were identical in both of these components in the 14 patients who had similar tumour response to HPET. We conclude that different clonality is a common reason for the differential response of co-existing MALToma and DLBCL of gastric DLBCL(MALT) to HPET and that immunohistochemical examination of BCL10 expression may help to identify the co-existence of these components.

An open, multi-centre, phase II clinical trial to evaluate the efficacy and safety of paclitaxel, UFT, and leucovorin in patients with advanced gastric cancer.

The aim of the study was to evaluate the response rate and safety of weekly paclitaxel (Taxol((R))) combination chemotherapy with UFT (tegafur, an oral 5-fluorouracil prodrug, and uracil at a 1 : 4 molar ratio) and leucovorin (LV) in patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Paclitaxel 1-h infusion at a dose of 100 mg m(-2) on days 1 and 8 and oral UFT 300 mg m(-2) day(-1) plus LV 90 mg day(-1) were given starting from day 1 for 14 days, followed by a 7-day period without treatment. Treatment was repeated every 21 days. From February 2003 to October 2004, 55 patients were enrolled. The median age was 62 years (range: 32-82). Among the 48 patients evaluated for tumour response, two achieved a complete response and 22 a partial response, with an overall response rate of 50% (95% confidence interval: 35-65%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 4.4 and 9.8 months, respectively. Major grade 3-4 toxicities were neutropenia in 25 patients (45%) and diarrhoea in eight patients (15%). Although treatment was discontinued owing to treatment-related toxicities in nine patients (16%), there was no treatment-related mortality. Weekly paclitaxel plus oral UFT/LV is effective, convenient, and well tolerated in treating patients with advanced gastric cancer.

Phase II study of weekly vinorelbine and 24-h infusion of high-dose 5-fluorouracil plus leucovorin as first-line treatment of advanced breast cancer.

We prospectively investigated the efficacy and safety of combining weekly vinorelbine (VNB) with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV) in the treatment of patients with advanced breast cancer (ABC). Vinorelbine 25 mg m(-2) 30-min intravenous infusion, and high-dose 5-FU 2600 mg m(-2) plus LV 300 mg m(-2) 24-h intravenous infusion (HDFL regimen) were given on days 1 and 8 every 3 weeks. Between June 1999 and April 2003, 40 patients with histologically confirmed recurrent or metastatic breast cancer were enrolled with a median age of 49 years (range: 36-68). A total of 25 patients had recurrent ABC, and 15 patients had primary metastatic diseases. The overall response rate for the intent-to-treat group was 70.0% (95% CI: 54-84%) with eight complete responses and 20 partial responses. All 40 patients were evaluated for survival and toxicities. Among a total of 316 cycles of VNB-HDFL given (average: 7.9: range: 4-14 cycles per patient), the main toxicity was Gr3/4 leucopenia and Gr3/4 neutropenia in 57 (18.0%) and 120 (38.0%) cycles, respectively. Gr1/2 infection and Gr1/2 stomatitis were noted in five (1.6%) and 59 (18.7%) cycles, respectively. None of the patients developed Gr3/4 stomatitis or Gr3/4 infection. Gr2/3 and Gr1 hand-foot syndrome was noted in two (5.0%) and 23 (57.5%) patients, respectively. Gr1 sensory neuropathy developed in three patients. The median time to progression was 8.0 months (range: 3-25.5 months), and the median overall survival was 25.0 months with a follow-up of 5.5 to 45+ months. This VNB-HDFL regimen is a highly active yet well-tolerated first-line treatment for ABC.

Phase II study of weekly oxaliplatin and 24-h infusion of high-dose 5-fluorouracil and folinic acid in the treatment of advanced gastric cancer.

To investigate the efficacy and safety of combining weekly oxaliplatin with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA) in treatment of patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Oxaliplatin 65 mg m(-2) 2-h intravenous infusion, and 5-FU 2600 mg m(-2) plus FA 300 mg m(-2) 24-h intravenous infusion, were given on days 1 and 8, repeated every 3 weeks. Between January 2001 through January 2002, 55 patients were enrolled. The median age was 64 years (range: 22-75). In all, 52 patients (94.5%) had recurrent or metastatic disease and three patients had locally advanced disease. Among 50 patients evaluable for tumour response, 28 patients achieved partial response, with an overall response rate of 56% (95% confidence interval (CI): 41.8-70.3%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 5.2 and 10.0 months, respectively, during median follow-up time of 24.0 months. Major grades 3-4 toxicities were neutropenia in 23 cycles (7.1%) and thrombocytopenia in 16 cycles (5.0%). Treatment was discontinued for treatment-related toxicities in nine patients (16.4%), of whom eight were due to oxaliplatin-related neurotoxicity. One patient (1.8%) died of neutropenic sepsis. This oxaliplatin-containing regimen is effective in the treatment of advanced gastric cancer. Except for neurotoxicity that often develops after prolonged use of oxaliplatin, the regimen is well tolerated.

Weekly gemcitabine plus 24-h infusion of high-dose 5-fluorouracil/leucovorin for locally advanced or metastatic carcinoma of the biliary tract.

Both gemcitabine and weekly 24-h infusion of high-dose 5-fluorouracil/leucovorin (HDFL) have shown promising antitumour activity for patients with locally advanced or metastatic carcinoma of the biliary tract (CBT). From April 1999 through December 2002, 30 patients with inoperable CBT were treated with gemcitabine 800 mg m(-2), intravenous infusion for 30 min, followed by 5-FU, 2000 mg m(-2) and leucovorin, 300 mg m(-2), intravenous infusion for 24 h, on day 1, 8 and 15, every 4 weeks. A total of 166 cycles were given (median of four cycles per patient, range 1-24 cycles). Response was evaluable in 28 patients and toxicity in 29 patients. Partial response was obtained in six patients, stable disease in 13, while progressive disease occurred in nine. The objective response rate was 21.4% (95% CI: 5.2-37.6%). The most common grade 3 or 4 toxicity was infection (nine patients). Other types of grade 3 or 4 toxicity included leucopenia (four patients), thrombocytopenia (three patients), anaemia (three patients), nausea/vomiting (two patients) and elevation of liver transaminases (three patients). As of 30 September 2003, the median progression-free survival was 3.7 months (95% CI: 2.8-4.6 months) and the median overall survival was 4.7 months (95% CI: 0.8-8.6 months). Our data suggest that weekly gemcitabine plus HDFL is modestly active with acceptable treatment-related toxicity for patients with advanced CBT.