Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.

Study of interleukin-6 and interleukin-8 levels in patients with neurological manifestations of dengue.

CONTEXT: Pro-inflammatory markers play a key role in the pathogenesis of various Flavivirus infection. AIM: In this study, we evaluated the role of these markers in neurological manifestations of dengue. SETTINGS AND DESIGNS: Consecutive dengue cases with different neurological manifestations who presented between August 2012 and July 2014 were studied in hospital-based case-control study. MATERIALS AND METHODS: Interleukin (IL-6) and IL-8 level were measured in serum and cerebrospinal fluid (CSF) of dengue cases with different neurological manifestations and also in age- and sex-matched controls. Level was analyzed with various parameters and outcomes. STATISTICAL ANALYSIS: Statistical analysis was done using SPSS version 16.0 by applying appropriate statistical methods. P < 0.05 considered statistically significant. RESULTS: Out of the 40 enrolled cases of dengue with neurological manifestations, 29 had central nervous system and 11 had peripheral nervous system (CNS/PNS) manifestations. In CNS group, both IL-6 and IL-8 (CSF and serum) were significantly elevated (P < 0.001), whereas CSF IL-6 (P = 0.008), serum IL-6 (P = 0.001), and serum IL-8 (P = 0.005) were significantly elevated in PNS group. CSF IL-6, serum IL-6, and IL-8 were significantly elevated in poor outcome patients in CNS group (P < 0.05). CSF IL-6 and IL-8 were significantly elevated in CSF dengue positive cases as compared to CSF negative patients (P < 0.05). Cytokine level was not significantly correlated with neuroimaging abnormality in CNS group. Nine patients died and the remainder recovered. CONCLUSION: Elevated level of IL-6 and IL-8 is associated with different neurological manifestations and poor outcome, but whether they are contributing to neuropathogenesis or simply a correlate of severe disease remains to be determined.

Cocaine Abuse: An Unusual Association.

Cocaine addiction is a common problem in the adolescent and the young adults, pharmacologic interventions to reverse the effects of which do not exist. Neurological complications of cocaine abuse, such as seizures, headache, ischemic or hemorrhagic stroke, or subarachnoid hemorrhage, can be disastrous as a result of uncontrolled vasoconstriction and vasculitic damage. The lone occurrence of subdural hematoma in the absence of any other intracranial hemorrhagic complication is rarely seen in patients of cocaine abuse. We wish to share our experience of one such patient who presented to us with an unusual combination of the widespread cerebral infarction and subdural hematoma.

Spinal cord involvement in tuberculous meningitis.

OBJECTIVES: To summarize the incidence and spectrum of spinal cord-related complications in patients of tuberculous meningitis. SETTING: Reports from multiple countries were included. METHODS: An extensive review of the literature, published in English, was carried out using Scopus, PubMed and Google Scholar databases. RESULTS: Tuberculous meningitis frequently affects the spinal cord and nerve roots. Initial evidence of spinal cord involvement came from post-mortem examination. Subsequent advancement in neuroimaging like conventional lumbar myelography, computed tomographic myelography and gadolinium-enhanced magnetic resonance-myelography have contributed immensely. Spinal involvement manifests in several forms, like tuberculous radiculomyelitis, spinal tuberculoma, myelitis, syringomyelia, vertebral tuberculosis and very rarely spinal tuberculous abscess. Frequently, tuberculous spinal arachnoiditis develops paradoxically. Infrequently, spinal cord involvement may even be asymptomatic. Spinal cord and spinal nerve involvement is demonstrated by diffuse enhancement of cord parenchyma, nerve roots and meninges on contrast-enhanced magnetic resonance imaging. High cerebrospinal fluid protein content is often a risk factor for arachnoiditis. The most important differential diagnosis of tuberculous arachnoiditis is meningeal carcinomatosis. Anti-tuberculosis therapy is the main stay of treatment for tuberculous meningitis. Higher doses of corticosteroids have been found effective. Surgery should be considered only when pathological confirmation is needed or there is significant spinal cord compression. The outcome in these patients has been unpredictable. Some reports observed excellent recovery and some reported unfavorable outcomes after surgical decompression and debridement. CONCLUSIONS: Tuberculous meningitis is frequently associated with disabling spinal cord and radicular complications. Available treatment options are far from satisfactory.

Outcome assessment in conservatively managed patients with cervical spine tuberculosis.

STUDY DESIGN: Cervical spine tuberculosis is a relatively less frequent form of spinal tuberculosis. Cervical spine tuberculosis has a greater propensity to involve the spinal cord and results in major sensory motor deficit. In this prospective study, we aimed to evaluate the clinical and imaging predictors of outcome in conservatively managed patients. METHODS: In this study, 42 patients of cervical spine tuberculosis were included. Patients were subjected to a detailed clinical evaluation and magnetic resonance imaging. Patients were treated with antituberculosis treatment and were followed up for 18 months. The Modified Barthel index (MBI) was used to assess the disability. Good outcome was defined as MBI >12 and poor outcome as MBI ⩽12. Clinical and imaging characteristics were used to analyze the predictors of outcome, using univariate and multivariate analysis. RESULTS: Four (9.5%) patients required surgery. Data from 38 patients, who were conservatively managed, were analyzed for predictors of outcome. Among conservatively managed patients, at presentation, 29 patients had an MBI score of ⩽12. At 18 months, the majority of patients (81.6%) had a good outcome. On univariate analysis, a duration of illness >3 months, a major motor deficit, bladder involvement, flexor spasms, significant cord compression and spinal extension of the abscess were significantly associated with a poor outcome. However, on multivariate analysis significant cord compression (P=0.003) and spinal extension (P=0.02) showed a significant correlation with a poor outcome. CONCLUSION: Medical management was effective in cervical spine tuberculosis. Patients with significant cord compression and spinal extension of the abscess showed poorer outcome.

Neurovascular antropylorus perineal transposition using inferior rectal nerve anastomosis for total anorectal reconstruction: preliminary report in humans.

BACKGROUND: Technical feasibility of inferior rectal nerve anastomosis to the anterior vagus branch of the perineally transposed antropyloric valve for total anorectal reconstruction has been previously demonstrated in cadavers. To the best of our knowledge, the present study is the first report of using this procedure in humans. METHODS: Eight patients [mean age 35.5 years (range 15-55 years); (male/female = 7:1)] underwent the procedure. The antropyloric valve with its anterior vagus branch was mobilized based on the left gastroepiploic arterial pedicle. The antral end was anastomosed to the distal colon. The anterior vagus nerve was anastomosed by epineural technique to the inferior rectal nerve in the perineum. A diverting proximal colostomy was maintained for 6 months. Anatomical integrity of the graft (on magnetic resonance imaging scans), its arterial pedicle (on computed tomography angiogram) and neural continuity (on ultrasound and pyloric electromyography) were assessed. Functional assessment was performed using barium retention studies, endoscopy, manometry and fecal incontinence scores. RESULTS: Tension-free end-to-end anastomosis of the anterior vagus nerve to the right (n = 7) and left (n = 1) inferior rectal nerve was achieved. An intact left gastroepiploic pedicle, a healthy graft and neural continuity were visualized on perineal ultrasound. Electromyographic activity was noticed on neural stimulation. Endoscopy and barium studies showed voluntary antral contraction and contrast retention, respectively, in all patients. The mean resting and squeeze pressures were 26.25 mmHg (range 16-62 mmHg) and 50.25 mmHg (range 16-113 mmHg), respectively. St. Mark's incontinence scores varied between 7 and 12. There were no major surgical complications. CONCLUSIONS: Pudendal (inferior rectal) innervation of the perineally transposed antropylorus in total anorectal reconstruction is feasible and may improve outcomes in selected patients with end-stage fecal incontinence.

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

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of prostate cancer was published in 2020. It was therefore decided, by both the ESMO and the Singapore Society of Oncology (SSO), to convene a special, virtual guidelines meeting in November 2021 to adapt the ESMO 2020 guidelines to take into account the differences associated with the treatment of prostate cancer in Asia. These guidelines represent the consensus opinions reached by experts in the treatment of patients with prostate cancer representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), 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 access restrictions in the different Asian countries. The latter were discussed when appropriate. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with prostate cancer across the different regions of Asia.

Using an EPID for patient-specific VMAT quality assurance.

PURPOSE: A patient-specific quality assurance (QA) method was developed to verify gantry-specific individual multileaf collimator (MLC) apertures (control points) in volumetric modulated arc therapy (VMAT) plans using an electronic portal imaging device (EPID). METHODS: VMAT treatment plans were generated in an Eclipse treatment planning system (TPS). DICOM images from a Varian EPID (aS1000) acquired in continuous acquisition mode were used for pretreatment QA. Each cine image file contains the grayscale image of the MLC aperture related to its specific control point and the corresponding gantry angle information. The TPS MLC file of this RapidArc plan contains the leaf positions for all 177 control points (gantry angles). In-house software was developed that interpolates the measured images based on the gantry angle and overlays them with the MLC pattern for all control points. The 38% isointensity line was used to define the edge of the MLC leaves on the portal images. The software generates graphs and tables that provide analysis for the number of mismatched leaf positions for a chosen distance to agreement at each control point and the frequency in which each particular leaf mismatches for the entire arc. RESULTS: Seven patients plans were analyzed using this method. The leaves with the highest mismatched rate were found to be treatment plan dependent. CONCLUSIONS: This in-house software can be used to automatically verify the MLC leaf positions for all control points of VMAT plans using cine images acquired by an EPID.

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

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of renal cell carcinoma was published in 2019 with an update planned for 2021. It was therefore decided by both the ESMO and the Singapore Society of Oncology (SSO) to convene a special, virtual guidelines meeting in May 2021 to adapt the ESMO 2019 guidelines to take into account the ethnic differences associated with the treatment of renal cell carcinomas in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with renal cell carcinoma representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), 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 access restrictions in the different Asian countries. The latter were discussed when appropriate.

Level-set segmentation of pulmonary nodules in megavolt electronic portal images using a CT prior.

PURPOSE: Pulmonary nodules present unique problems during radiation treatment due to nodule position uncertainty that is caused by respiration. The radiation field has to be enlarged to account for nodule motion during treatment. The purpose of this work is to provide a method of locating a pulmonary nodule in a megavolt portal image that can be used to reduce the internal target volume (ITV) during radiation therapy. A reduction in the ITV would result in a decrease in radiation toxicity to healthy tissue. METHODS: Eight patients with nonsmall cell lung cancer were used in this study. CT scans that include the pulmonary nodule were captured with a GE Healthcare LightSpeed RT 16 scanner. Megavolt portal images were acquired with a Varian Trilogy unit equipped with an AS1000 electronic portal imaging device. The nodule localization method uses grayscale morphological filtering and level-set segmentation with a prior. The treatment-time portion of the algorithm is implemented on a graphical processing unit. RESULTS: The method was retrospectively tested on eight cases that include a total of 151 megavolt portal image frames. The method reduced the nodule position uncertainty by an average of 40% for seven out of the eight cases. The treatment phase portion of the method has a subsecond execution time that makes it suitable for near-real-time nodule localization. CONCLUSIONS: A method was developed to localize a pulmonary nodule in a megavolt portal image. The method uses the characteristics of the nodule in a prior CT scan to enhance the nodule in the portal image and to identify the nodule region by level-set segmentation. In a retrospective study, the method reduced the nodule position uncertainty by an average of 40% for seven out of the eight cases studied.

Cardiovascular complications and its relationship with functional outcomes in Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) is a monophasic disease characterized by acute polyradiculoneuropathy. AIM: This study investigated cardiovascular complications in patients with GBS and their relationship with outcomes. DESIGN AND METHODS: We included 96 patients, who were diagnosed with GBS according to Brighton case definitions. All enrolled patients were evaluated according to a predetermined algorithm, which included nerve conduction studies, cerebrospinal fluid analysis, electrocardiography, 2D echo, cardiac markers and autonomic function testing. RESULTS: We enrolled a total of 96 patients. The mean age of patients was 35.75 ± 17.66 years. Furthermore, 54.2% of patients developed cardiovascular complications, of which changes in electrocardiography (ECG) findings (50%), hypertension (28.12%), labile hypertension (12.5), tachycardia (26.04), bradycardia (13.54%) and a fluctuating heart rate (HR) (11.46) were common. Other cardiovascular complications seen in GBS patients were increased pro-BNP (26.04%), raised troponin T levels (3.12%), acute coronary syndrome (2.08%), heart failure (2.08%) and abnormal 2D echo findings (8.33%). The results of the univariate analysis revealed that a history of preceding infection, a Medical Research Council sum score, neck muscle weakness, facial nerve involvement, bulbar involvement, respiratory failure, cardiovascular complications, autonomic dysfunction, acute motor sensory axonal neuropathy subtype and baseline Hughes score were significantly (P < 0.005) associated with poor outcomes. However, none of these factors were found to be independently associated with poor outcomes in the multivariate analysis. CONCLUSION: A considerable number of patients with GBS developed cardiovascular complications and it needs attention.

Isolation and characterization of plasma membrane fractions from garfish Lepisosteus osseus olfactory nerve.

Garfish Lepisosteus osseus olfactory nerve, because of its large size and the unusually high concentration of axonal membrane, is an excellent source of axonal membrane. A procedure is described for the isolation of two types of plasma membranes from the nerve which are obtained in yields of about 20 mg (fraction I) and 1.5 mg (fraction II) per g of wet nerve. Both membrane fractions consist mostly of rounded membrane vesicles, with a unit membrane thickness of approximately 7.5 nm. The two membrane fractions are different in their lipid to protein ratios, Na-K ATPase activities, polypeptide patterns on sodium dodecyl sulfate (SDS) gel electrophoresis, and fatty acid compositions. They have similar phospholipid composition. On the basis of the relative concentration of axonal and Schwann cell plasma membranes in the nerve, the Na-K ATPase activities of the two membrane fractions and a comparison of the properties of the membrane fractions to those of squid and lobster nerve membrane preparations, fraction I seems to be the axonal membrane and fraction II the Schwann cell plasma membrane. Fraction I has a low protein to lipid ratio. Its polypeptide pattern on SDS gel appears to be much more complex as compared to that of fraction II membrane.

Corticosteroids (dexamethasone versus intravenous methylprednisolone) in patients with tuberculous meningitis.

As inflammatory changes play an important role in the neuropathogenesis of the disease, adjunctive corticosteroid treatment may be of benefit in tuberculous meningitis. In an open-label study in India, 97 patients with such meningitis were randomized into a control group, a dexamethasone group (with the drug given intravenously once a day for 4 weeks, and then orally, once daily, for another 4 weeks) and a methylprednisolone group (with the drug given intravenously once a day for 5 days). All the patients also received standard anti-tuberculosis drugs. The primary outcome measure was death or severe disability 6 months after the randomization, with a modified Rankin scale used to assess each patient's level of disability. The other outcome measures investigated were deterioration in vision, focal neurological deficits and new-onset seizures. Six patients (one of those given dexamethasone, three of those given methylprednisolone and two of those in the control group) were lost to follow-up. Although each corticosteroid was associated with a reduction in death or disability, this reduction did not reach statistical significance in either the dexamethasone group (relative risk of death=0.6, with a 95% confidence interval of 0.29-1.2; P>0.05) or the methylprednisolone group (relative risk of death=0.7, with a 95% confidence interval of 0.4-1.4; P>0.05), probably because of the small sample sizes. Among the patients who died within 10 months of randomization, the mean time to death (post-randomization) was 8.8 months in the dexamethasone group, 8.2 months in the methylprednisolone group, and 7.1 months in the control group (P>0.05). The prevalence of impaired vision, among all the patients evaluated, decreased from 41.8% at baseline to 29.9% (among the survivors) 6 months later. Adverse events were similar and equally reported in the two corticosteroid groups. Larger trials are still needed to determine if dexamethasone and/or methylprednisolone are useful in the treatment of tuberculous meningitis, at least in India.

Does histoid leprosy represent a locally hyperimmune variant of lepromatous leprosy?

BACKGROUND: Histoid leprosy is a subtype of leprosy with distinct clinical presentation and histologic features. It accounts for <4% of leprosy cases. The exact location of histoid leprosy along the immune spectrum and its relation to other subtypes is unclear. AIM: To evaluate the local immune phenomenon which define histoid leprosy. DESIGN: Parallel skin biopsies from histoid lesions and from unremarkable skin in patients with histoid leprosy were evaluated and the histologic findings compared. METHODS: Formalin fixed, paraffin embedded tissue sections from lesional and non-lesional biopsies were assessed for changes in epidermis and dermis; type and extent of infiltrate, presence or absence of pseudocapsule and associated reactions. Bacillary index was evaluated using Wade Fite stain for lepra bacilli. RESULTS: Amongst 208 leprosy cases, six cases of histoid leprosy were identified (2.88%). The cases showed presence of nodules, patches and plaques overlying clinically unremarkable skin. Fourteen skin biopsies were evaluated of which the lesional biopsies showed equal proportion of fusocellular, fusocellular epithelioid and fusocellular-vacuolated histology. A greater circumscription was noted in lesional biopsies; however the cellular content of the infiltrate was similar in lesional and non-lesional biopsies. A case of erythema nodosum leprosum in histoid leprosy was also seen. CONCLUSIONS: Ours is the first study comparing normal and lesional skin in histoid leprosy. Though the histoid lesions appear to have a derivation from lepromatous leprosy, the local histologic and clinical alterations may be a result of heightened local immunity or reactive local modifying factors.

Ophthalmological manifestation in patients of tuberculous meningitis.

BACKGROUND: Vision impairment, blindness in particular is a devastating complication in patients with tuberculous meningitis. However, information regarding ophthalmological manifestation and its impact on vision is sparse in the literature. This study evaluated the spectrum of ophthalmological manifestations in tuberculous meningitis, including retinal nerve fiber layer thickness assessment by optic coherence tomography and its correlation with visual and clinical outcome. METHODS: This was a prospective observational study done from October 2015 to March 2017. Consecutive patients of tuberculous meningitis, diagnosed as per consensus case definition were included in the study. The patients were divided into two categories: uncomplicated and complicated tuberculous meningitis. Clinical evaluation, cerebrospinal fluid examination and contrast enhanced MRI of brain was done. Detailed ophthalmological evaluation including optic coherence tomography was done in all patients. All the patients were followed for 6 months. The primary outcome was blindness or low vision after 6 months. The secondary outcome was death or severe disability after 6 months. It was defined as modified Barthel index (MBI) ≤ 12 at 6 months (including disability plus death). Appropriate statistical analysis was done. RESULTS: Out of 101 patients of tuberculous meningitis, 47 patients of TBM belonged to uncomplicated category, while 54 patients were of complicated group. The visual impairment was present in 24 out of 101 (23.76%) patients out of which 20 (19.8%) patients had low vision while 4 (3.96%) had blindness. The visual impairment was more evident in complicated group, low vision 0.03 (1.2-31.5). The most common abnormality on fundus examination was papilledema (22.8%). The complicated group had more incidence <0.0001 (19.6-48). Optic atrophy was found in three patients while choroid tubercles were found in eight patients (all complicated TBM group). RNFL thinning was noted in 10 patients in both the eyes. On univariate analysis, presence of diplopia at baseline, impairment of color vision at baseline, visual impairment at baseline, cranial nerve VIth involvement, optic atrophy and papilledema at baseline, RNFL thinning, abnormal VEP and baseline MBI were associated with poor visual outcome. On multivariate analysis, none of the factors were found to be independently associated with poor visual outcome. On univariate analysis, many factors including baseline MRC staging, altered sensorium, seizure, hemiparesis, basal exudates, infarcts, optochiasmaticarachnoiditis, visual impairment at baseline were found to be associated with poor clinical outcome at 6 months. On multivariate analysis, presence of seizure (P = 0.047, odds ratio = 78.59, 95% confidence interval (1.07-578.72)) was the only factor found to be independently associated with poor outcome. CONCLUSION: Wide spectrum of ophthalmological manifestation was observed in patients of tuberculous meningitis. The visual impairment was more evident in complicated tuberculous meningitis. Ophthalmological findings like optic atrophy, papilledema and RNFL thinning were associated with poor visual outcome on univariate but not multivariate analysis. Visual impairment at baseline, among other factors was associated with poor clinical outcome on univariate analysis, whereas seizure was the only factor independently associated with poor outcome on multivariate analysis.

Camphor ingestion: an unusual cause of seizure.

Camphor is a pleasant smelling cyclic ketone with propensity of causing neurologic side-effects especially seizures. We report two patients who after inadvertent consumption of camphor experienced an episode of generalized tonic clonic seizure. These cases highlight the importance of enquiring any intake of material (medicinal or otherwise) in every patient presenting with seizure.

Drug resistance and associated genetic mutations among patients with suspected MDR-TB in Uttar Pradesh, India.

SETTING: Programmatic Management of Drug-Resistant Tuberculosis (PMDT) programme in 32 districts of Uttar Pradesh (UP), India. OBJECTIVE: To provide epidemiological status of multidrug-resistant tuberculosis (MDR-TB) and associated microbial genetic mutations among suspected cases in UP. DESIGN: We retrospectively studied and tested using line-probe assay (LPA) 4895 retreatment patients with suspected MDR-TB who were enrolled for PMDT during 2012-2015. The demographic characteristics of cases, LPA-determined drug resistance, the genetic mutation profile, trends in drug resistance over the study period as well as the comparative performance of LPA and phenotypic drug susceptibility testing (DST) were analysed. RESULTS: MDR-TB and rifampicin-resistant TB (RR-TB) were confirmed in respectively 34.5% and 40.3% cases. The RR-TB detection rate (a valid proxy for MDR-TB) initially declined during the study period. Age â©¿30 years and implemented MDR-TB suspicion criteria were independent predictors for RR-TB (P < 0.01). LPA indicated predominant distribution of S531L (1483/1970, 75.3%) and S315T1 (1981/2116, 93.6%) mutations in the rpoB and katG genes, respectively, and had >94.0% agreement with phenotypic DST in determining rifampicin/isoniazid resistance. CONCLUSION: MDR-TB prevalence in retreatment cases is very high, highlighting the need to reduce the development and transmission of drug-resistant TB.

Phase I chemotherapy study of biochemical modulation of folinic acid and fluorouracil by gemcitabine in patients with solid tumor malignancies.

PURPOSE: This phase I biochemical modulation study evaluated the maximum-tolerated dose (MTD), toxicity, and effectiveness of the combination of folinic acid (FA)/fluorouracil (5-FU) followed by escalated dose levels of gemcitabine (FFG) in patients with advanced solid tumors. PATIENTS AND METHODS: Patients were refractory to primary treatment and/or without effective treatment options. Twenty-eight patients received an intravenous (IV) infusion of FA 100 mg/m(2) over 1 hour and a 5-FU 450 mg/m(2) IV bolus in the middle of the FA infusion. After the FA infusion, gemcitabine was administered at a steady rate of infusion of 10 mg/m(2)/min over initially 30 minutes and with increases of an additional 15 minutes at each given level. One cycle consisted of six weekly treatments followed by a 2-week rest. RESULTS: The MTD of gemcitabine was established at 900 mg/m(2) given over 90 minutes. Eight patients of 21 with metastatic colorectal cancer achieved responses (one complete response; seven partial responses), for a response rate of 38%. Responses were seen across the gemcitabine doses of 300 to 900 mg/m(2). One patient had prior treatment with FA/5-FU for advanced disease. Patients with colorectal carcinoma had a median survival of 18 months, and the patient with lung carcinoma has been alive for 24+ months. CONCLUSION: The combination chemotherapy of FFG was well tolerated and may benefit patients with advanced colorectal carcinoma. A phase II evaluation in this patient population is in progress.