Cepharanthine action in preventing obesity and hyperlipidemia in rats on a high-fat high sucrose diet.

Background: It was demonstrated that cepharanthine (CEP), derived from Stephania cepharantha hayata, is a potent inhibitor of the ABCC10 transmembrane protein. It is approved to be a natural product or remedy. The present study focuses on investigating whether cepharanthine effectively reduces hyperlipidemia and obesity in an experimental hyperlipidemic rat model. Method: Four groups of Wistar rats were assigned randomly to the following groups: a high-fat high sucrose diet (HFHS), normal-fat diet (NFD), HFHS plus cepraranthine (10 mg/kg) (HFHS-C), and a HFHS diet with atorvastatin (HFHS-A). The responses of rats were observed on the basis of serum and hepatic biochemical parameters, food intake, and body weight after CEP treatment, and assessing the histopathological modifications by the optical microscope in the liver and its cells. Results: Significant improvement in the serum total cholesterol (TC), serum triglycerides (TG), and serum low-density lipoprotein (LDL) levels were observed following CEP treatment. We have also observed significant improvement in the structure of liver tissue and reduced-fat droplets in the cytoplasm. Moreover, CEP had a significant effect in preventing the gain in body weight of animals, and food intake was not significantly affected. Conclusion: Our research results revealed that CEP significantly improved dyslipidemia and prevented the accumulation of fatty deposits in the rats' liver tissue fed an HFHS diet. In addition, CEP exerted an anti-obesity effect.

Histopathological and biochemical assessment of liver damage in albino Wistar rats treated with cytotoxic platinum compounds in combination with 5-fluorouracil.

INTRODUCTION: Chemotherapy-induced hepatotoxicity in cancer patients often results in cessation of therapy and prevents completion of the treatment plan. The entire pathological description and comparison of hepatic damage induced by oxaliplatin or cisplatin in combination with 5-fluorouracil (5-FU) is not adequately reported. This study reports histopathological assessment of hepatotoxicity of a non-tumor bearing organ in rats treated with 5-FU, oxaliplatin and cisplatin (CDDP). MATERIAL AND METHODS: Changes in hepatic biochemical profile of 36 albino Wistar rats equally divided into different treatment groups with cisplatin, oxaliplatin, 5-FU, cisplatin plus 5-FU and oxaliplatin plus 5-FU were compared with a group of rats treated with normal saline (control group). At the end of treatments, hepatic tissues were taken for blinded histopathological assessment by light microscopy. RESULTS: Serum glutamate pyruvate transaminase and serum glutamic-oxaloacetic transaminase levels were disrupted in rats treated with 5-FU alone and in combination with cisplatin or oxaliplatin. Hepatocellular injuries, e.g. sinusoidal dilatation, venular fibrosis and centrilobular vein injury induced by oxaliplatin were intensified in treatment groups also receiving 5-FU, manifested as massive architectural distortion, periportal fibrosis, hepatic cord degeneration and cystic lesions with demarcated margins. Hepatocellular degenerative sequence and abnormally dilated central hepatic vein was shown in the cisplatin plus 5-FU treatment group with hemorrhage and blood filled sinusoids. CONCLUSIONS: Oxaliplatin-associated cystic lesions were intensified in rats treated with a combination of 5-FU and oxaliplatin.

Neuroprotective effect of diclofenac on chlorpromazine induced catalepsy in rats.

Neuroinflammation plays a key role in progressive degeneration of dopaminergic cells. Upregulation of prostaglandins and free radicals formation are involved in the mechanisms of cell death in Parkinson's disease (PD). The present study aimed to investigate the neuroprotective effect of diclofenac against chlorpromazine (CPZ) induced catalepsy and motor impairment in mice. Adult Wistar rats treated with CPZ (3 mg/kg/day, IP) were orally dosed with diclofenac and L-dopa/carbidopa for 21 days. Catalepsy was measured after 21 days of dosing by using standard bar test at 30, 60, 90, 120 and 180 min then motor performances were assessed via open field test and wire hanging test. Histopathological investigation and determination of dopamine (DA) and 3,4-Dihydroxyphenylacetic acid (DOPAC) levels of rat's brain was also carried out. We found that CPZ treated group exhibited reduced motor impairment after 21 days of treatment in open field and wire hanging test (P < 0.01) as compared to control group. The cataleptic scores of CPZ treated rats were also significantly increased (P < 0.01) after 21 days of chronic dosing, however diclofenac treated groups showed significant reduction in cataleptic scores with improved motor performances. Histopathology of CPZ treated rats showed marked degeneration with architecture distortion in the mid brain region. Dopaminergic degeneration is confirmed by neurochemical results that showed reduced amount of dopamine and DOPAC levels in mid brain. Moreover, histopathological slides of diclofenac treated rats showed improved architecture with reduced gliosis of mid brain region as well as improved dopamine and DOPAC levels were achieved after 21 days dosing of diclofenac. Taken together, the present work provide an evidence that diclofenac ameliorated behavioral performances by mediating neuroprotection against CPZ induced PD via preventing dopaminergic neuronal cell death.

Buspirone attenuates methylphenidate-induced growth inhibition.

Methylphenidate is effective in the treatment of attention deficit hyperactivity disorder (ADHD) in children and adults, but its long term use can cause potential adverse effect on growth rate and variable effects on appetite. Previous studies have shown that long term administration of psychostimulant drugs increases the effectiveness of somatodendritic 5-hydroxytryptamine (5-HT)-1A receptors. Repeated administration of buspirone attenuates the effectiveness of somatodendritic 5-HT1A receptors. The present study was designed to test the hypothesis that co-administration of buspirone may attenuate methylphenidate-induced effects on growth rate and food intake. Growth rate was calculated weekly in terms of change in body weight as percentage of preceding week's body weight and food intake was calculated weekly by subtracting the amount of food left in the hopper from the amount of food placed in the hopper as % in preceding week mg/gm of body weight after long-term administration of methylphenidate, buspirone and their co-administration. Long term oral administration of methylphenidate at a dose of 2.0 mg/kg/day decrease growth rate, but co-administration of buspirone at a dose of 10 mg/kg/day attenuates effect of methylphenidate on growth rate however food intake was significantly greater in all treated groups after 3 weeks of treatment. It is suggested that buspirone may oppose methylphenidate-induced growth inhibition by decreasing the sensitivity of somatodendritic 5-HT1A receptors. These findings may help to extend future therapeutics in ADHD.

Young coconut water ameliorates depression via modulation of neurotransmitters: possible mechanism of action.

In the current era, plants are frequently tested for its antidepressant potential. Therefore young coconut water, a commonly used plant based beverage, was selected to explore its antidepressant potential. Rodents were selected for this study and forced swim test was conducted to explore antidepressant activity. Analysis of brain biogenic amines using high performance liquid chromatography coupled with electrochemical detection and potentiation of noradrenaline toxicity model were also incorporated in this study to demonstrate probable antidepressant mechanism of action. Coconut water was administered orally at the dose of 4 ml/100 g. Young coconut water showed highly significant increase in struggling time (p < 0.001) in forced swim test. This suggests antidepressant effect of young coconut water. In noradrenaline toxicity model, it was observed that young coconut water is not a good adrenergic component as its lethality percentage in this test was observed 0 % unlike imipramine which showed lethality of 100 %. High performance liquid chromatography-electrochemical detection of rodent's brain revealed decline in 5-hydroxytryptamine, noradrenaline and dopamine, with concomitant decline in metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, homovanillic acid and increase in 5-hydroxyindoleacetic acid/5-hydroxytryptamine ratio. Findings from the exploration of monoamines suggest antidepressant effect of young coconut water via homeostasis of monoamines synthesis.

Coconut water of different maturity stages ameliorates inflammatory processes in model of inflammation.

AIM: Coconut water is a natural beverage that is a part of daily diet of many people. This study was designed to explore the anti-inflammatory activity of coconut water of different maturation stages (young and mature) with rat paw edema model of inflammation using plethysmometer. METHODOLOGY: For this study, albino rats were selected and divided into four equal groups (10 rats in each group). Group 1 was set as control and administered distilled water 1 ml orally; Groups 2 and 3 were treated with young and mature coconut water, respectively, at 4 ml/100 g dose orally. Group 4 was treated with the standard drug (ibuprofen) at 400 mg/70 kg. 0.1 ml of 1% w/v acetic acid was administered in the subplantar tissue of rat paw 30 min after oral treatments of groups. Plethysmometer was used to measure rat paw edema. RESULTS: Results revealed that both coconut water possess significant anti-inflammatory activity (P < 0.001). In comparison to control, percent inhibition by young coconut water was 20.22%, 35.13%, 42.52%, and 36% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (42.52%) was observed in the second phase of the inflammatory process. On the other hand, percent inhibition by mature coconut water was 18.80%, 25.94%, 24.13%, and 18.66% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (25.94%) was observed in the first phase of the inflammatory process. CONCLUSIONS: This study strongly suggests the use of young coconut water for potent anti-inflammatory effect and mature coconut water for moderate anti-inflammatory effect.

Clinical Features of Oxaliplatin Induced Hypersensitivity Reactions and Therapeutic Approaches.

Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan.

Attenuation of methylphenidate-induced sensitization by co-administration of buspirone.

Methylphenidate, which inhibit dopamine transporter is effective in the treatment of ADHD (attention deficit hyperactivity disorder), but long term use of this drug is often associated with addiction and dependence. Locomotor sensitization development to psychostimulants like methylphenidate is an important contributor to drug abuse induced by psychostimulants. Different studies have shown that long term administration of drugs of abuse increases the effectiveness of 5-hydroxytryptamine (5-HT)-1A somatodendritic receptors. Repeated buspirone administration reduces the effectiveness of 5-HT1A somatodendritic receptors. This study was designed to determine that buspirone co-administration may reduce methylphenidate-induced sensitization. The motor activity was compared by using familiar and novel environments after long-term administration of methylphenidate, buspirone and their co-administration. Long term oral administration of methylphenidate at a dose of 2.0 mg/kg/day enhanced motor activity in home cage i.e. activity of familiar environment monitored at alternate day. Locomotor enhancing effects of methylphenidate were augmented on 13th day of drug administration suggesting sensitization induced by the drug. The sensitization effects were significant in home cage monitored on alternate day and also in an open field monitored weekly. Buspirone co-administration at a dose of 10 mg/kg/day prevented methylphenidate-induced sensitization. It is suggested that the sensitization development to methylphenidate may oppose by buspirone co-administration due to the reduction in the sensitivity of 5-HT1A somatodendritic receptors. These findings may help extend future therapeutics in ADHD.

Efficacy of combination herbal product (Curcuma longa and Eugenia jambolana) used for diabetes mellitus.

The purpose of this research was to evaluate the efficacy of a combination herbal product that is traditionally used for managing diabetes mellitus. Herbal drug contains Curcuma longa and Eugenia jambolanain the ratio of 1:1. It was orally administered at the dose of 1082 mg/70 kg twice a day for a period of 6 weeks to alloxan induced diabetic rats and compared with glibenclamide (standard). The effects of drug were observed at intervals, with respect to random and fasting glucose levels. HbA1C was also monitored after the drug treatment to monitor the overall diabetic effect. Results revealed that the combination of two herbs significantly reduced fasting and random glucose levels with HbA1C of less than 6% (p<0.001) in comparison to diabetic control. The control of fasting blood glucose levels by herbal combination is similar to the standard drug, glibenclamide (p<0.05). Random glucose levels by herbal combination is better than standard drug after one week and six weeks of treatment (p<0.01 and p<0.001 respectively) and similar after third week of treatment (p<0.05). Also, herbal drug combination showed HbA1C closer to the standard drug. It shows that this herbal combination can be of potential benefit in managing diabetes mellitus in future.

Attenuation of methylphenidate-induced tolerance on cognition by buspirone co-administration.

Methylphenidate as a psycho stimulant drug has been prescribed in neuropsychiatric disorders to increase cognition and attention therefore is a medication of choice for attention-deficit/hyperactivity disorder however long-term administration of central nervous system stimulant produces tolerance on cognitive behavior. Previously it has been shown that long-term psychostimulant administration increases somatodendritic 5HT-1A receptors effectiveness. Repeated buspirone administration attenuates 5-HT1A soma to dendritic receptors effectiveness. This study was designed to determine that buspirone co-administration may reduce methylphenidate-induced tolerance on cognitive behavior. Cognitive effects were compared by using water maze and passive avoidance test weekly after long-term administration of methylphenidate, buspirone and their co-administration. Methylphenidate at a dose of 2.0mg/kg/day in rats initially improve memory but after long-term treatment produce tolerance on cognitive behavior this effect is more pronounce in case of spatial working memory of water maze test than passive avoidance learning memory. However oral buspirone co-administration at a dose of 10mg/kg/day prevents methylphenidate-induce tolerance on cognition. It is suggested that buspirone may oppose methylphenidate-induced cognitive tolerance by reducing the sensitivity of 5-HT 1A soma to dendritic receptors. These findings may help to extend future therapeutics in ADHD.

Determination of heavy metal contents by atomic absorption spectroscopy (AAS) in some medicinal plants from Pakistani and Malaysian origin.

This study depicts a profile of existence of heavy metals (Cu, Ni, Zn, Cd, Hg, Mn, Fe, Na, Ca, and Mg) in some important herbal plants like (H. Integrifolia, D. regia, R. communis, C. equisetifolia, N. oleander, T. populnea, M. elengi, H. schizopetalus, P. pterocarpum) from Pakistan and an antidiabetic Malaysian herbal drug product containing (Punica granatum L. (Mast) Hook, Momordica charantia L., Tamarindus indica L., Lawsonia inermis L.) using atomic absorption spectrophotometer. Heavy metals in these herbal plants and Malaysian product were in the range of 0.02-0.10 ppm of Cu, 0.00-0.02 ppm of Ni, 0.02-0.29 ppm of Zn, 0.00-0.04 ppm of Cd, 0.00-1.33 ppm of Hg, 0.00-0.54 ppm of Mn, 0.22-3.16 ppm of Fe, 0.00-9.17 ppm of Na, 3.27-15.63 ppm of Ca and 1.85-2.03 ppm of Mg. All the metals under study were within the prescribed limits except mercury. Out of 10 medicinal plants/product under study 07 were beyond the limit of mercury permissible limits. Purpose of this study is to determine heavy metals contents in selected herbal plants and Malaysian product, also to highlight the health concerns related to the presence of toxic levels of heavy metals.

Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats.

Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose (8mg/kg/day) and at low dose (2mg/kg/day) of methylphenidate in 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed.

Evaluation of Iyengariastellata for its hypolipidemic and hepatoprotective activity.

Cholesterol is believed to be the major regulator involved in the formation and progression of atheroma plaque. Seaweeds are known to possess enormous biological activities. They contain variety of active constituents, which have pharmacological significance. The objective of this study is to explore hypolipidemic and hepatoprotective activities of the brown seaweed Iyengariastellata. Ethanolic extract of seaweed was suspended in distilled water and administered orally at 10mg/200g body weight to rabbits for 30 days and total lipid level, cholesterol, triglycerides, HDL, LDL, VLDL, alkaline phosphatase, SGPT, SGOT, Gamma GT were assessed. The results showed overall decrease in lipid profile whereas Iyengariastellata increased liver enzymes except SGPT which was decreased highly significantly, since SGPT is more specific indicator of liver injury, decreased value of SGPT indicates that Iyengariastellata toxicity is less severe and reversible with marked hypolipidemic effect, but during the course of ingestion of the seaweed the liver enzymes must be carefully monitored to ensure liver safety.

Gastrointestinal adverse effects in advanced colorectal carcinoma patients treated with different schedules of FOLFOX.

BACKGROUND: To assess the frequency and severity of gastrointestinal adverse effects in advanced colorectal carcinoma patients treated with four different schedules of FOLFOX. MATERIALS AND METHODS: Patients (median age 61 years) who underwent surgery were included in the study. All had measureable disease at CT scan, ultrasonography or clinical examination. Toxicity was graded on a scale of 1-5 according to the general grade definition of CTC v2.0. The severity of adverse effects (Grade 3 and 4) assessed in each treatment arm was compared. RESULTS: Differences between the incidence rates of 3 and 4 toxicity and all grades of toxicity for all parameters in GI toxicity were very highly significant (p<0.001). Severe gastrointestinal symptoms of toxicity were noted with FOLFOX7 (oxaliplatin 130 mg/m2). Grade 3 diarrhea was reported in 25% patients and grade 4 diarrhea in 4% in the FOLFOX7 treatment arm. Grade 2 vomiting was very frequently reported in the FOLFOX4 treatment arm (oxaliplatin 85mg/m2). Grade 2 stomatitis was reported in 42% patients treated with mFOLFOX6 (oxaliplatin 100mg/m2). Differences in the incidence rate of nausea, diarrhea and stomatitis among all treatment arms of FOLFOX were significant (p<0.05) . CONCLUSIONS: Severe diarrhea is associated with FOLFOX7 treatment. No grade 3 or 4 GI toxicity was reported in patients of the mFOLFOX6 arm.

Adverse effects on cardiovascular status and lipid levels of albino Wistar rats treated with cisplatin and oxaliplatin in combination with 5 Fluorouracil.

The study was designed to comparatively assess direct damages on cardiac tissues and aorta associated with abnormalities in lipid profile and cardiac biomarkers induced by two platinum cytotoxic compounds with and without 5FU (5Fluorouracil) in rats. Albino Wistar rats were treated with 5FU (15mg/kg), cisplatin (0.8mg/kg) and oxaliplatin (0.8mg/kg) in different dosing schedules. The changes in the lipid levels, CPK and Tropinin I levels, following treatment with single and combination schedules of CDDP, 5FU and Oxaliplatin were compared with the control group maintained on normal saline. Changes in LDL and cholesterol levels were highly significant in cisplatin and oxaliplatin treated rats. Myofibrillar loss and vascular wall thickening was seen in cisplatin treatment groups in the acute model of toxicity. The damages were mild but progressive. Tropinin I levels were raised well above diagnostic risk levels in the delayed model of toxicity in the rats treated with oxaliplatin in combination of 5FU, indicative of definite cardiotoxic potential of oxaliplatin in combination of 5FU mimicking the FOLFOX regimen.

Chamomile tea: herbal hypoglycemic alternative for conventional medicine.

Chamomile is considered as one of the oldest and also documented as medicinal plant. It has shown to be an anti-inflammatory, astringent and antioxidant especially in floral part since ancient times. Recent studies reported that chamomile has potential to lower blood sugar levels in hyperglycemia. In the present study we have investigated the pharmacological effects of chamomile tea on fasting and post prandial glucose levels and HbA1C in blood of diabetic rats (alloxan induced) and the results were compared with glibenclamide as standard. Statistical analysis was performed using SPSS. It has been observed in our study that it has reduced progressively the fasting and post prandial blood sugar levels, significantly in alloxan induced diabetic rats particularly on day 30 and 60. It also reduced the level of HbA1C significantly at the end of the study and the effects were similar to that of the standard group. Chamomile tea administration has also controlled the reduction in weight in diabetic rats as compared to diabetic control and the results were not very much different from standard. Results from the present study indicate that chamomile tea have a glucose lowering effect in diabetic rats so its daily consumption can be potentially useful in hyperglycemia and it can be used as a substitute of conventional drug treatment. Further studies are necessary to elucidate the exact molecular mechanism involved in anti-diabetic action of chamomile.

Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX.

The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different (P < 0.05), whereas frequency and onset of peripheral neuropathy were highly significant (P < 0.01) in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles) even at low doses (85 mg/m(2)), whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130 mg/m(2)) after few treatment cycles.

Comparative cardiac toxicity in two treatment schedules of 5-FU/LV for colorectal carcinoma.

The purpose of the study is evaluation and assessment of parameters of cardiac toxicity in patients subjected to 5-FU based chemotherapy. Cardiac morbidity is a reported outcome in different 5FU/LV regimens; however none of them are definite or proximate. The bimonthly regimen of high dose leucovorin is reported to be less toxic and more effective as compared to the monthly regimen of low dose leucovorin. We report the detailed assessment of few cardiac parameter of toxicity in patients of advanced colorectal carcinoma subjected to two Schedules of high and low dose Folinic Acid, 5-Fluorouracil, bolus and continuous infusion. The correlation of elevated cardiac biomarkers, angina and hypertension is comparatively assessed in patients with normal general status, hyperglycemia and known cardiac disorders subjected to two different 5FU based chemotherapeutic regimen.

Comparative assessment of skin and subcutaneous toxicity in patients of advanced colorectal carcinoma treated with different schedules of FOLFOX.

OBJECTIVE: The study was designed to assess the skin and subcutaneous toxicity in patients with advanced colorectal carcinoma treated with four different schedules of FOLFOX. METHODS: The patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study as per specified inclusion criteria. Toxicity was graded according to CTC v2.0. The frequency of grade 3 and 4 adverse effects were comparatively assessed in each treatment arm. RESULTS: Very severe toxicity was attributed to the FOLFOX7 schedule. The difference between the incidence rate of grade 4 toxicity with all other grades for all parameters of skin and subcutaneous toxicity was highly significant (p=0.00<0.001). Grade 4 hand and foot syndrome was reported only in the FOLFOX7 treatment arm. The most frequent adverse symptom of skin and subcutaneous toxicity reported in the patients treated with modified schedule of FOLFOX was pruritus (grade 1). Frequency and onset of skin and subcutaneous toxic symptoms like alopecia (p=0.000), nail discoloration (p=0.021) and pruritis (p=0.000) was significantly different in each FOLFOX treatment arm. A few cases of oncholysis were also reported in the FOLFOX7 treatment arm. Hand and foot syndrome was fast progressing in patients with grade 1 toxicity. CONCLUSION: Higher frequency and severity of hand and foot syndrome and pruritus wasa found in the FOLFOX7 treatment arm. Skin and subcutaneous toxicity was comparatively low in the FOLFOX6 treatment arm.

High and low dose folinic acid, 5-fluorouracil bolus and continuous infusion for poor-prognosis patients with advanced colorectal carcinoma.

OBJECTIVE: Evaluation and assessment of response rate, duration and toxicity in patients subjected to 5-FU based chemotherapy. BACKGROUND: The therapeutic ratio shifts with different 5FU/LV regimens and none yet serve as the internationally accepted Gold Standard. A bimonthly regimen of high dose leucovorin is reported to be less toxic and more effective than monthly low dose regimens. We here compare therapeutic responses and survival benefit of the two regimens in poor prognosis patients with advanced colorectal carcinoma. PATIENTS AND METHODS: A total of 35 patients with histologically confirmed colorectal carcinoma were subjected to de Gramont and Mayo Clinic regimen. Nineteen patients were treated with high dose folinic acid (200 mg/m2), glucose 5%, 5-FU (400 mg/m2) and 22 hr. CIV (600 mg/m2) for two consecutive days every two weeks. These patients had failed responses to previous chemotherapy and were above sixty years of age with poor general status. Sixteen patients (six below 60 years) with progressive disease were subjected to low dose folinic acid (20 mg/m2)for five days, 5FU(425 mg/m2) injection bolus for 5 days, every five weeks. An initial evaluation was made in sixty days and responders were reevaluated at sixty days interval or earlier in case of clinical impairment. Based on positive prognosis, the therapy was continued. Evaluation of treatment response was made on the basis of WHO criteria. RESULTS: The response rate was 44% in thirty four evaluable patients, with 4 complete responses (11.8%) and 11 (32.4%) partial responses. The two schedules were well tolerated, whereas, mild toxicity without WHO Grade ≥ 2 events was assessed. The response duration was extended (12 months) in a few patients with age above sixty years treated by high dose bimonthly regimen of 5FU/LV. CONCLUSION: The regimens are safe and effective in advanced colorectal carcinoma patients with poor general status.