The combination of oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX) has recently been shown to be beneficial in advanced colorectal and gastric cancers. The side effects of this regimen include neutropenia, diarrhea and neurosensory toxicity. However, case reports on the pulmonary toxicities of this regimen are very limited. Especially, the development of pulmonary fibrosis has never been cited in the literature. Herein is reported the case of a patient treated with oxaliplatin, 5-fluorouracil and leucovorin combination chemotherapy in whom pulmonary fibrosis developed, but which improved after steroid pulse therapy.
Diarrhea ; Drug Therapy* ; Drug Therapy, Combination ; Fluorouracil* ; Humans ; Leucovorin* ; Neutropenia ; Pulmonary Fibrosis* ; Stomach Neoplasms

PURPOSE: There are few therapeutic options in patients with colorectal cancer that have progressed or recurred following 5-fluorouracil (5-FU) based therapy. We evaluated the efficacy and toxicity of oxaliplatin, 5-FU, leucovorin (Mayo clinic regimen) in 5-FU pretreated advanced colorectal cancer patients. MATERIALS AND METGODS: Twenty-eight patients were enrolled in this study between January 1999 and May 2001. Patients were treated with oxaliplatin 150 mg/m2 on day 1 as a 2-hr infusion and 5-FU 425 mg/m2, leucovorin 20 mg/m2, bolus for 5 days. Treatment courses were repeated in 4-week intervals. RESULTS: The objective response rate was 25% for 28 assessable patients, all cases registered a partial response. Eleven patients (39%) demonstrated stable disease, and ten (36%) progressed. The median response duration was 5.5 months, and the median time to progression was 6.3 months. The median overall survival time was 13.5 months from the start of the chemotherapy. From the 120 cycles analyzed, grade 3,4 hematologic toxicities included neutropenia: 1.6%, and thrombocytopenia: 1.6%. The frequent grade 3.4 non-hematologic adverse reactions were nausea/vomiting (25.0%), diarrhea (14.3%), stomititis (3.6%), and neuropathy (3.6%). There were no treatment-related deaths. CONCLUSION: This phase II study had relatively higher toxicity than previous studies, and did not show an increased significant response rate. These high levels of toxicity suggest that the study treatment combination of oxaliplatin with a full dose Mayo clinic regimen arm is no feasible. Therefore, this regimen will be discontinued and a safer regimen will be adopted.
Arm ; Colorectal Neoplasms* ; Diarrhea ; Drug Therapy ; Drug Therapy, Combination ; Fluorouracil* ; Humans ; Leucovorin* ; Neutropenia ; Thrombocytopenia

PURPOSE: This study was performed to estimate the response rate and toxicity of a combination chemotherapy, which included infusional 5-Fluorouracil, Leucovorin and Docetaxel in the treatment of patients with an advanced gastric carcinoma. MATERIALS AND METHODS: Twenty two advanced gastric cancer patients, with a bidimensionally measurable or an evaluable disease, were enrolled in this study. The patients received a 5-fluorouracil 1, 000 mg/m2 intravenous (IV) 24 hour infusion (Day 1~3), leucovorin 20 mg/m2 (Day 1~3) and docetaxel 75 mg/m2 intravenously (Day 2) every 3 weeks. RESULTS: The overall response rate was 45.0%. The median duration of response was 10.0 weeks (range: 4~24), the median time to response was 8 weeks (range: 8~20) the median time to progression was 30.0 weeks (95% CI: 16.3~43.2) and the median overall survival duration was 36.0 weeks (95% CI: 1.7~70.2). The median cumulative dose of 5-fluorouracil were 316.2 mg/m2/week and docetaxel was 23.9 mg/m2/week. WHO grade III, IV neutropenia, thromocytopenia and anemia occurred in 50.0%, 4.5% and 4.5% of patients, respectively. There were no occurrence of WHO grade III and IV nausea, vomiting, mucositis, conspitation, diarrhea, or neurotoxicity. CONCLUSION: This chemotherapy regimen, including infusional 5-fluorouracil, leucovorin and docetaxel was an active agent against advanced gastric cancer patients, especially for previous chemotherapy naive patients.
Anemia ; Diarrhea ; Drug Therapy ; Drug Therapy, Combination ; Fluorouracil* ; Humans ; Leucovorin* ; Mucositis ; Nausea ; Neutropenia ; Stomach Neoplasms* ; Vomiting

Shenling Baizhu San is a classic prescription for replenishing Qi to invigorate the spleen and dispelling dampness to check diarrhea, which mainly treats the syndrome of spleen deficiency and heavy dampness. With the pharmacological effects of regulating immune system, improving lung function and gastrointestinal function, and resisting oxygen, tumor, and inflammation, Shenling Baizhu San is commonly used in modern clinical practice to treat chronic obstructive pulmonary disease, pulmonary fibrosis, bronchial asthma, irritable bowel syndrome, ulcerative colitis, chronic diarrhea, and diabetic, etc. This paper summarized the chemical constituents, pharmacological effects, and clinical application of Shenling Baizhu San in recent years, and predictively analyzed the quality markers of Shenling Baizhu San according to the "five principles" of Q-marker. The Q-markers of Shenling Baizhu San involved ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, pachymic acid, dehydrotumulosic acid, batatasin Ⅰ, batatasin Ⅲ, diosgenin, liensinine, neferine, luteolin, quercetin, glycerol trioleate, β-sitosterol, platycodin D, glycyrrhizic acid, glycyrrhetinic acid, liquiritin, pipecolinic acid, atractylenolide Ⅰ, atractylenolide Ⅲ, and bornyl acetate, which provided references for the quality control and follow-up research of Shenling Baizhu San.
Humans ; Ginsenosides/therapeutic use* ; Drugs, Chinese Herbal/pharmacology* ; Colitis, Ulcerative/drug therapy* ; Diarrhea/drug therapy*

OBJECTIVE: To compare the clinical efficacy between herbal-moxa plaster and moxa-box moxibustion for diarrhea type irritable bowel syndrome (IBS-D) of spleen and kidney yang deficiency. METHODS: Eighty patients with IBS-D of spleen and kidney yang deficiency were randomly divided into a herbal-moxa plaster group and a moxa-box moxibustion group, 40 cases in each group. The patients in the two groups were treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 24⁺), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Yinlingquan (SP 9), and Taixi (KI 3), etc. In addition, the patients in the herbal-moxa plaster group were treated with herbal-moxa plaster (Wenyang Fuzheng ointment, composed of prepared monkshood, prepared evodia rutaecarpa, dried ginger, cinnamon, etc.) at Shenque (CV 8), Guanyuan (CV 4), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Shenshu (BL 23) and Shangjuxu (ST 37); the patients in the moxa-box moxibustion group were treated with moxa-box moxibustion at the same acupoints as the herbal-moxa plaster group. The acupuncture-moxibustion treatment was provided once every other day for 4 weeks (14 treatments). Before and after treatment, the scores of clinical symptom of TCM, irritable bowel syndrome (IBS) symptom severity scale (IBS-SSS) and IBS quality of life scale (IBS-QOL) were compared between the two groups, and the clinical efficacy was evaluated. RESULTS: Compared with those before treatment, each item scores and total scores of clinical symptom of TCM, and IBS-SSS scores in the two groups were reduced after treatment (P<0.05). The abdominal bloating score, stool frequency score and total score of clinical symptom of TCM as well as IBS-SSS score in the herbal-moxa plaster group were lower than those in the moxa-box moxibustion group (P<0.05). Compared with those before treatment, the IBS-QOL scores in the two groups were increased after treatment (P<0.05), and the IBS-QOL score in the herbal-moxa plaster group was higher than that in the moxa-box moxibustion group (P<0.05). The total effective rate was 92.5% (37/40) in the herbal-moxa plaster group, which was higher than 85.0% (34/40) in the moxa-box moxibustion group (P<0.05). CONCLUSION On the basis of conventional acupuncture treatment, herbal-moxa plaster could effectively improve the clinical symptoms and quality of life in IBS-D patients of spleen and kidney yang deficiency, and its efficacy is superior to that of moxa-box moxibustion.
Humans ; Spleen ; Irritable Bowel Syndrome/drug therapy* ; Quality of Life ; Yang Deficiency/drug therapy* ; Kidney ; Diarrhea

PURPOSE: To determine the activity and the toxicity associated with a low dose regimen of leucovorin (LV) plus 5-fluorouracil (5-FU) combined with oxaliplatin every two weeks (modified FOLFOX 4) as a salvage therapy for advanced gastric cancer patients. MATERIALS AND METHODS: Between December 2003 and December 2004, 33 patients were enrolled in this study. The patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion on the first day plus LV 20 mg/m2 over 10 minutes. Subsequently, the patients were given a 5-FU bolus 400 mg/m2 followed by a 22-hour continuous infusion of 600 mg/m2 on days 1~2. The treatment was repeated at 2 week intervals. RESULTS: The median age of the patients was 50 years (range: 31~74), 82% (27/33) had the Eastern Cooperative Oncology Group performance status was 0 and 1. Of the 30 patients who could be evaluated for their tumor response, 8 achieved a partial response, with an overall response rate of 26.7% (95% confidence interval (CI): 20.5~32.7%). Fifteen patients (50%) showed stable disease and 7 patients (23.3%) progressed during the course of treatment. The median time from the start of chemotherapy to progression was 3.5 months (95% CI: 2.6~4.4 months) and the median overall survival time was 7.9 months (95% CI: 5.9~9.9 months). The major grade 3/4 hematological toxicity encountered included neutropenia (45.4%) and thrombocytopenia (3.0%). Neutropenic fever occurred during only 2 of the 178 cycles. The most common non-hematological toxicity encountered was grade 1/2 nausea/vomiting, which occurred in 18.2% of patients, diarrhea in 12.1% and neuropathy in 15.2%. There were no treatment related deaths. CONCLUSIONS: The modified FOLFOX 4 regimen appears to be a safe and effective salvage therapy for advanced gastric cancer patients.
Diarrhea ; Drug Therapy ; Fever ; Fluorouracil* ; Humans ; Leucovorin* ; Neutropenia ; Salvage Therapy* ; Stomach Neoplasms* ; Thrombocytopenia

PURPOSE: The physiologic mechanism of chemotherapy induced emesis is poorly understood, but recently it is thought to be mediated by serotonergic (5-hydroxytryptamine-3 or 5-HT3) receptars. 5-HT3 is released by enterochromaffin cells in the gastrointestinal tract, which peaks 2-6 hours after the start of chemotherapy. In this study, the granisetron, an antiemetic agent, was given over 2-hour from the start of cisplatin administration to synchronize the peak level of the drug with that of 5-HT3 release. MATERIALS AND METHODS: Chemotherapy-naive patients undergoing their first cycle of cisplatin ( > 60 mg/m)-based chemotherapy were included. One milligram of granisetron was given intravenously 15 minutes before the start of cisplatin as a loading dose, then 2 mg was given over 2-hour starting with the cisplatin. RESULTS: 24 of 25 patients were evaluable for efficacy and safety. Fifteen (62.5%) of the 24 evaluable patients had advanced gastric carcinoma and 21 (87.5%) received FP (5-FU/ Cisplatin) combination chemotherapy. The complete response rate for acute and delayed vomiting/retching was 58.3% (10/24) and 33.3% (8/24), respectively. The median latency time to first vomiting or retching was 20.3 hours. Side effects were tolerable, but central nervous symptoms (dizziness, headache, or anxiety) and diarrhea were frequently noted. CONCLUSION: Two-hour infusion of granisetron with the beginning of cisplatin showed no superior efficacy compared with historical controls that used bolus administration of granisetron, but somewhat more frequent central nervous system and gastrointestinal symptoms were observed.
Central Nervous System ; Cisplatin* ; Diarrhea ; Drug Therapy ; Drug Therapy, Combination ; Enterochromaffin Cells ; Gastrointestinal Tract ; Granisetron* ; Headache ; Humans ; Vomiting

BACKGROUND: Irinotecan is an active agent in colorectal cancer, producing 30~40% response rates when combined with 5-fluorouracil and leucovorin in metastatic colorectal cancer as first line therapy, however, the best combination schedules are not determined yet. We investigated the efficacy and toxicity of irinotecan combined with bolus 5-fluorouracil, continuous infusion 5-fluorouracil, and high-dose leucovorin every two weeks (LV5FU2 regimen) in recurrent or metastatic colorectal cancer in Korean patients. METHODS: Twenty-two patients with measurable diseases previously untreated with chemotherapy other than adjuvant chemotherapy for advanced colorectal cancer were enrolled onto this study and received the study drugs between June 2000 and December 2001. Treatment consisted of irinotecan (180 mg/m2 over two hours on day 1) followed by leucovorin (200 mg/m2 over two hours), bolus 5-fluorouracil 400 mg/m2 and continuous infusion of 5-fluorouracil (600 mg/m2 over next 22 hours) on day 1 and 2. Chemotherapy was repeated every two weeks until progressive disease. RESULTS: Of the 20 patients evaluable for response, 8 partial responses were observed with a response rate of 40%. Six additional patients achieved stable disease as their best response, and six progressed. The median time to progression was 5.0 months and median overall survival was 17.3 months. The most frequently observed grade 3~4 toxicities were neutropenia (18%) and diarrhea (4.8%). Two mortalities occurred, though not clearly related to treatment, before the end of chemotherapy. CONCLUSION: Irinotecan combined with LV5FU2 regimen was effective in advanced colorectal cancer with manageable side effects. Caution should be paid to elderly and poor performance patients to prevent treatment related mortality and morbidity.
Aged ; Appointments and Schedules ; Chemotherapy, Adjuvant ; Colorectal Neoplasms* ; Diarrhea ; Drug Therapy ; Drug Therapy, Combination* ; Fluorouracil* ; Humans ; Leucovorin* ; Mortality ; Neutropenia

This article highlights the role of prucalopride in the management of chronic constipation based upon the principles of meta-analysis using data reported in the published randomized, controlled trials. Sixteen randomized, controlled trials on 3943 patients reported the effectiveness of prucalopride in patients with chronic constipation. Prucalopride successfully increased the frequency of spontaneous bowel movements per week in all variable doses of 1 mg (standardized mean difference [SMD], 0.42 [95% CI, 0.18-0.66; P = 0.006]), 2 mg (SMD, 0.34 [95% CI, 0.11-0.56; P = 0.003]), and 4 mg (SMD, 0.33 [95% CI, 0.22-0.44; P = 0.00001]). The risks of adverse events or side effects such as headache, abdominal cramps, excessive flatulence, dizziness, diarrhea, and rash were higher (odds ratio, 1.70 [95% CI, 1.27 to -2.27; P = 0.0004]) in prucalopride group. Prucalopride is clinically a beneficial pharmacotherapy for chronic constipation and its routine use may be considered in patients with chronic simple laxative-resistant constipation.
Colic ; Constipation* ; Diarrhea ; Dizziness ; Drug Therapy ; Exanthema ; Flatulence ; Headache ; Humans ; Laxatives

PURPOSE: To determine the activity and toxicities of low dose leucovorin (LV) plus fluorouracil (5-FU) regimen, combined with oxaliplatin every two weeks (modified FOLFOX 4), as a first-line therapy for patients with metastatic colorectal cancer. MATERIALS AND METHODS: Between March 2001 and August 2003, fifty-five patients were enrolled in this study. Patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion at days 1 plus LV 20 mg/m2 over 10 minutes, followed by 5-FU bolusa 400 mg/m2 bolus and 22 hour continuous infusion of 600 mg/m2 5-FU at day 1~2. This treatment was repeated in 2 week intervals. RESULTS: The objective response rate was 40% on an intent-to-treatment analysis. Three patients (6%) demonstrated a complete response and nineteen patients (38%) showeda partial response. Sixteen patients (32%) showed a stable disease and eleven patients (22%) progressed during the course of the treatment. The median time to progression and overall survival time wereas 6.6 months (95% CI: 4.98~8.02 months) and the median overall survival time was 17.0 months (95% CI: 9.15~24.85 months) from the start of the chemotherapy, respectively. A total of 275 cycles were analyzed for toxicity. Major hematologic toxicities included grade 1~2 anemia (23.5%), neutropenia (25.3%) and thrombocytopenia (10.6%). There were only 2 cycles of neutropenic fever. The most common non- hematologic toxicities were grade 1~2 nausea/vomiting (10.9%), diarrhea (9.1%) and grade 1 neuropathy (18.0%). There was no treatment related death. CONCLUSION: The modified folfox 4 regimen is safe and effective regimen as a first-line therapy in advanced colorectal cancer patients.
Anemia ; Colorectal Neoplasms* ; Diarrhea ; Drug Therapy ; Fever ; Fluorouracil* ; Humans ; Leucovorin* ; Neutropenia ; Thrombocytopenia