levoleucovorin and Anorexia

A phase II study of S-1 plus leucovorin (LV) given in a 4-week schedule (2 weeks' administration followed by 2 weeks' rest) for patients with untreated metastatic colorectal cancer (mCRC) showed that the combination was effective, but grade 3 toxicities (diarrhea, stomatitis and anorexia) occurred at a relatively high rate. In this phase II study, we evaluated the efficacy and safety of a 2-week schedule of S-1 plus LV. Patients with mCRC received oral S-1 (40-60 mg) and LV (25 mg) twice daily for 1 week, followed by 1 week's rest. Treatment was repeated until disease progression or unacceptable toxicity. The primary endpoint was response rate. The pharmacokinetics of S-1 and LV in Chinese patients were evaluated on day 1 of the first cycle. Seventy-three patients were enrolled in Japan and China. Of 71 eligible patients, the response rate was 53.5%, and the disease control rate was 83.1%. Median progression-free survival and median overall survival were 6.5 and 24.3 months, respectively. The incidences of grade 3 toxicities were diarrhea 8.3%, stomatitis 8.3%, anorexia 2.8% and neutropenia 9.7%. There were no treatment-related deaths. The pharmacokinetics profiles of S-1 plus LV in Chinese patients were similar to those in Japanese patients. This 2-week schedule of S-1 plus LV showed good efficacy and better tolerability than the 4-week schedule. This therapy will be the base regimen for mCRC to be added by other cytotoxic or molecular-targeted drugs. The optimized treatment schedule for S-1 plus LV was 1 week on and 1 week off.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; China; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Japan; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Stomatitis; Survival Analysis; Tegafur; Treatment Outcome

The purpose of this phase II study was to explore the efficacy and safety of an alternating regimen consisting of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (mFOLFOX6) plus bevacizumab, and folinic acid, 5-FU and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer.. Fifty-two patients with metastatic colorectal cancer received an alternating regimen consisting of four cycles of mFOLFOX6 plus bevacizumab followed by four cycles of FOLFIRI plus bevacizumab until disease progression. The primary endpoint was progression-free survival.. The median age was 60 years (range 37-75 years). Median progression-free survival was 14.2 months (95 % confidence interval [CI] 10.6-16.3) and median overall survival was 28.4 months (95 % CI 22.6-39.1). The overall response rate was 60.0 % (95 % CI 45.2-73.6). Regarding toxicity, the commonest grade 3-4 hematological adverse events were neutropenia (34.6 %) and leukopenia (7.7 %), and the commonest grade 3-4 non-hematological adverse events were anorexia (13.5 %), fatigue (9.6 %), nausea (9.6 %), and vomiting (9.6 %). Bevacizumab-related grade 3-4 adverse events included hypertension (1.9 %) and thrombosis (1.9 %).. An alternating regimen consisting of mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab is an effective and well-tolerated first-line chemotherapy combination for patients with metastatic colorectal cancer.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Fatigue; Female; Fluorouracil; Humans; Hypertension; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Survival Rate; Thrombosis; Vomiting

Previous reports of the influence of UGT1A1 gene polymorphisms on the pharmacokinetics of irinotecan metabolism have not assessed Asian patients treated with FOLFIRI plus bevacizumab for advanced and recurrent colorectal cancer. Twenty-one Japanese colorectal cancer patients received intravenous FOLFIRI (bolus irinotecan, folinic acid, and fluorouracil followed by 46-hour fluorouracil infusion) followed by bevacizumab (5 mg/kg) in Cycle 1. In Cycle 2, patients received bevacizumab followed by FOLFIRI. The regimen was in 2-week cycles. The area under-the-curves ratio (AUC0-last) (Cycle 2/Cycle 1) was determined from plasma concentrations of irinotecan and metabolites (SN-38, SN-38G). Safety, efficacy, and drug-drug interactions were analyzed. Median observation period was 7.8 months; median number of cycles 15. Drug-drug interactions were evaluated in eight patients without irinotecan dose reduction. Mean AUC0-last ratios (with/without bevacizumab) of irinotecan, SN-38, and SN-38G were 0.959, 0.927, and 0.931 respectively. Response rate was 65%; median progression-free survival 16.4 months. Response occurred in four patients with, and nine without, UGT1A1 polymorphism. No significant differences occurred between efficacy, safety, or polymorphism status. This cohort showed no differences in safety or efficacy compared to previous reports. Bevacizumab did not affect the pharmacokinetics of irinotecan and its metabolites, irrespective of UGT1A1 polymorphism status.

Topics: Adult; Aged; Anorexia; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Asian People; Bevacizumab; Camptothecin; Colorectal Neoplasms; Diarrhea; Drug Interactions; Female; Fluorouracil; Glucuronosyltransferase; Humans; Leucovorin; Male; Middle Aged; Nausea; Neutropenia; Treatment Outcome

In our previous randomized controlled trial, the addition of S-1 to gemcitabine for advanced pancreatic cancer did not prolong overall survival (OS) significantly, despite its higher response rate and longer progression-free survival (PFS). Leucovorin is known to enhance efficacy of S-1, and we conducted this phase I trial of combination therapy of gemcitabine, S-1 and leucovorin (GSL).. Patients with advanced pancreatic cancer who had received no prior chemotherapy were eligible for this study. Gemcitabine was administered at an escalating dose of 600, 800 and 1,000 mg/m(2) over 30 min on day 1, and oral S-1 at a dose of 40 mg/m(2) twice daily and oral leucovorin at a dose of 25 mg twice daily on days 1-7, every 2 weeks. A standard "3 + 3" phase I dose escalation design was utilized.. Fifteen patients were enrolled across three dose levels. Three patients developed DLTs: two patients in level 1 (grade 3 anorexia in 1 and grade 3 anorexia, stomatitis and diarrhea in 1) and one patient in level 2 (grade 3 deep vein thrombosis). No DLT was observed in level 3. Response rate and the disease control rate were 33 and 93 %, respectively. The median PFS and OS were 5.4 and 16.6 months. Ten of 12 patients (83 %) with elevated CA19-9 at baseline had a ≥ 50 % decline.. RD of gemcitabine in GSL was determined as 1,000 mg/m(2). GSL was well tolerable and showed promising results in advanced pancreatic cancer.

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Diarrhea; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Gemcitabine; Humans; Leucovorin; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Stomatitis; Survival Analysis; Tegafur; Treatment Outcome; Venous Thrombosis

This study aimed to compare the efficacy and toxicity of weekly paclitaxel plus S-1 with weekly paclitaxel plus 5-fluorouracil in treating advanced gastric cancer as first line regimen. The primary end-point was disease control rate (DCR).. Patients with advanced or recurrent gastric cancer were randomly assigned to an experimental arm or a control arm. The experimental arm's dosage schedule was paclitaxel 60 mg/m2 (intravenous infusion) on days 1, 8 and 15 and S-1 80-120 mg/d (oral administration) on days 1-14. Control arm patients were given the same paclitaxel, combined with 5-fluorouracil 500 mg/m2 (continuous intravenous infusion) on days 1-5; and leucovorin 20 mg/m2 (intravenous infusion) on days 1-5. All schedules were repeated every 28 d.. A total of 240 patients were enrolled and equally randomised into two arms. The overall response rate and DCR of the experimental arm was non-inferior to that of the control arm both in the per-protocol set and the full analysis set. The secondary end-point median progression-free survival (PFS) of the experimental and control arms was 153 and 129 d, with the hazard ratio of 0.641 (95% CI: 0.473-0.868, P = 0.004). The hazard ratio of the time to treatment failure of the two arms was 1.449 (95% CI: 0.705-2.980, P = 0.229). The six-month PFS rates of both arms were similar (31.3% versus 31.8%, P = 0.94). Cox regression analysis indicated that only treatment regimen and age were independent predictive factors for PFS. The most common adverse events were haematological and gastrointestinal. The rates of grade 3-4 adverse events were not significantly different between the two study arms and were mostly lower than 5%.. Weekly paclitaxel combined with S-1 is an active and well-tolerated regimen, supporting the view that S-1 can be an alternative for infusional 5-fluorouracil for advanced gastric cancer.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Leucovorin; Leukopenia; Male; Middle Aged; Multivariate Analysis; Nausea; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome; Young Adult

We investigated the efficacy and safety of oral Uracil/tegafur (UFT) with leucovorin and mitomycin C (MMC) as third-line treatment for patients with extensively pretreated metastatic colorectal cancer (mCRC). This was a multicenter, prospective phase II study. Patients received MMC 7 mg/m² on day 1 and UFT 300 mg/m² with leucovorin 90 mg, both divided into three daily doses, on days 1-28 every 5 weeks. All patients had failed prior treatment with irinotecan, oxaliplatin, fluoropyrimidine, bevacizumab, and cetuximab. The primary endpoint was tumor control rate evaluated after 2 cycles. Twenty-one patients were included: median age was 66 years (41.1-87.8 years). Tumor control rate was observed in 26.7% of the 15 patients evaluable for response. Median overall survival was 6.4 months. Grade 3 adverse events were asthenia, anorexia, and vomiting. In patients with mCRC who have progressed after as many as two prior therapies, the combination of UFT/leucovorin and MMC is safe and may produce a short stabilization of disease in approximately 25% of patients.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Asthenia; Colorectal Neoplasms; Drug Combinations; Drug Monitoring; Female; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Mitomycin; Neoplasm Grading; Salvage Therapy; Survival Analysis; Tegafur; Tumor Burden; Uracil

Two phase III studies revealed an oral UFT/Leucovorin (LV) regimen, in which the drugs are taken for 28 consecutive days every 35 days, which proved to be equivalent to an infusional 5-fluorouracil/LV regimen for metastatic colorectal cancer (CRC). The weekday-on/weekend-off schedule for UFT, which is taken for 5 consecutive days followed by 2 drug-free days,has been reported to be safe and to have good feasibility. In the present study, we investigated the weekday-on/weekend-off schedule for UFT/LV in 54 patients with CRC. The median administration period was 8 months. Ten patients (19%) showed grade 2 or more severe adverse reactions. One of them had grade 3 diarrhea and anorexia. Grade 2 anemia was observed in 9 cases (19%) and grade 2 leucopenia was in 2 cases (4%). Myelotoxicity was mild. These results suggested that the adverse reactions in the weekday-on/weekend-off schedule for UFT/LV are less severe than the conventional UFT/LV schedule reported previously. Antitumor effects and survival benefits of the two schedules should be evaluated by a phase III study.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Tegafur; Uracil

Infusional fluorouracil (5-FU) and leucovorin (LV) with oxaliplatin is one of the current standard regimens for the treatment of patients with metastatic colorectal cancer. Weekly bolus 5-FU with high-dose LV (Roswell Park Memorial Institute Regimen: RPMI) is the most commonly used regimen in Japan. The objectives of this study were to determine the recommended dose (RD) of RPMI combined with oxaliplatin and to evaluate the toxicity and efficacy at the RD.. The subjects were 18 patients with metastatic colorectal cancer. Oxaliplatin (85 mg/m2) was given intravenously over 2 h on days 1 and 15 with l-LV (250 mg/m2) given intravenously over 2 h and 5-FU as an intravenous bolus on days 1, 8, and 15. This treatment was repeated every 4 weeks. The dose of 5-FU was escalated from 400 mg/m2 (level 1) to 500 mg/m2 (level 2).. A total of 14 patients received level 1, and 4 received level 2. Three of the patients had dose-limiting toxicity (DLT) in cycle 1 of level 2 (grade 3 thrombocytopenia, grade 4 neutropenia and grade 2 neutropenia in one patient each), requiring that treatment was delayed for longer than 7 days. None of the 14 patients given level 1 had DLT or grade 3 or 4 gastrointestinal toxicity. Sensory neuropathy occurred in all patients. Objective response rates were 61% in the 18 patients studied and 64% at level 1. The median time to progression was 171 days, and the median overall survival time was 603 days in the 18 patients studied.. Oxaliplatin (85 mg/m2) with weekly bolus 5-FU (400 mg/m2) and high-dose l-LV (250 mg/m2) is recommended for further phase III studies in patients with metastatic colorectal cancer.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System Diseases; Rectal Neoplasms; Remission Induction; Survival Rate

A Phase I study of UFT plus l-LV was conducted in 29 patients (pts) with G.I. cancer on a multicenter cooperative study. UFT and l-LV were given orally in two divided doses for 28 consecutive days, followed by a 14 day-rest period. UFT was fixed in three doses, 250, 313 and 375 mg/m2/day, and l-LV was increased in dose from 25 to 50 and to 100 mg/body/days. Dose-limiting toxicities were anorexia, diarrhea, and nausea/vomiting. The maximum tolerated dose of UFT was 375 mg/m2/day, and l-LV 25 mg/body/day. Severe myelotoxicity was not observed. There were three responders (PR) out of 21 pts with measurable disease at UFT doses of 313 mg/m2/day and l-LV 50 and 100 mg/body/day. Responses observed were abdominal mass (rectal ca), liver metastasis (pancreas ca) and metastasis of liver and lymph-node (gastric ca). As a result of pharmacokinetics, plasma concentrations of 5-methyl-THF were maintained > 1.0 microM for over 5 hours that was considered to have a modulating effect on the plasma concentration. In doses of 50 mg and 100 mg/body/day of l-LV. No accumulations in plasma were observed in patient treated in 28 days by l-LV/UFT therapy. It was suggested UFT and l-LV did not interfere with each other's absorption. A Phase II study is recommended, with doses of 313 mg/m2/day of UFT and 50 or 100 mg/body/day of l-LV.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Gastrointestinal Neoplasms; Humans; Leucovorin; Male; Middle Aged; Nausea; Stomach Neoplasms; Tegafur; Uracil; Vomiting

From October 1995 to June 1997, 19 chemotherapy-naive patients with pathology-proven locally advanced or metastatic biliary tract carcinomas (BTC) were enrolled. The regimen consisted of 5-fluorouracil (5-FU) 2600 mg/m2 and leucovorin (LV) 150 mg by weekly 24 h infusion for 6 weeks and followed by a 2 week break. The treatment was terminated if disease progressed, the patient refused or unacceptable toxicity occurred. All patients required a Port-A catheter insertion and were treated at outpatient clinics by portable infusion pumps. There were 12 males and seven females with a median age of 62 years (range 45-77). The primary tumor sites were nine intrahepatic cholangiocarcinomas (CC), three perihilar CC, one distal BTC and six gallbladder cancers. A total of 179 chemotherapy sessions were given with a mean of 9.5 (range 2-18). Eighteen patients were evaluable for response. The response rates were: 33% (six of 18) partial response (PR), 39% (seven of 18) stable disease (SD) and 28% (five of 18) progressive disease (PD). All of the patients were evaluable for toxicity. The most common toxicities were mild fatigue (nine of 19, 47%), loss of appetite (nine of 19, 47%), skin hyperpigmentation (five of 19, 26%) and diarrhea (two of 19, 11%). Only one patient had grade IV myelotoxicity with sepsis but without treatment-related death. The median time to progression was 4 months. The overall median survival time was 7.0 months. The median survival time of the PR was not reached, SD was 8.0 months and PD 3.5 months. In conclusion, weekly high-dose 5-FU with LV by 24 h infusion in an outpatient setting for patients with BTC is effective, only mildly toxic and deserves further study.

Topics: Aged; Anorexia; Antidotes; Antimetabolites, Antineoplastic; Biliary Tract Neoplasms; Bone Marrow; Diarrhea; Dose-Response Relationship, Drug; Drug Combinations; Fatigue; Female; Fluorouracil; Humans; Hyperpigmentation; Infusion Pumps; Leucovorin; Male; Middle Aged; Skin; Treatment Outcome; Vomiting

Uracil and tegafur in a 4:1 molar concentration ratio (UFT; Bristol-Myers Squibb, Wallingford, CT) has broad anti-tumor activity for cancers arising from the gastrointestinal tract. However, there are no published data regarding the efficacy of leucovorin-modulated UFT in patients with pancreatic cancer. The objective of this trial was to determine the activity and evaluate the toxicity of UFT plus oral calcium leucovorin in patients with advanced pancreatic adenocarcinoma.. Fourteen patients with advanced measurable adenocarcinoma of the pancreas were enrolled onto the trial. Patients received 300 mg/m2/d UFT plus 90 mg/d leucovorin administered orally in divided doses every eight hours for 28 days repeated every 35 days. Objective tumor response was evaluated after two courses of therapy.. Fourteen patients were evaluable for response and toxicity. No objective responses were seen. The median (range) time to progression and survival were 14 (1.6-37), and 15 (1.9-62) weeks, respectively. Toxicity was mild with severe (grade 3 or 4) hyperbilirubinemia, pain, diarrhea, transaminitis, venous thrombus, weakness, renal failure, confusion, and edema/ascites seen in three (21%), one (7%), two (14%), one (7%), one (7%), one (7%), one (7%), one (7%), and two (14%) patients, respectively.. In the 14 patients evaluable, UFT 300 mg/m2/d plus oral leucovorin 90 mg/d administered for 28 days did not demonstrate anti-tumor activity against advanced pancreatic adenocarcinoma; however, this oral regimen was well tolerated and devoid of neutropenia, significant oral mucositis or diarrhea.

Topics: Adenocarcinoma; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Leucovorin; Male; Nausea; Pancreatic Neoplasms; Tegafur; Treatment Outcome; Uracil

A randomized comparative study of surgical adjuvant chemotherapy using dl-leucovorin (dl-LV) and 5-fluorouracil (5-FU) (FL-therapy) with CDDP, 5-FU, and dl-LV (PFL-therapy) was conducted. The following were the administration schedules: Arm A was 13 mg/m2 of CDDP, 300 mg/m2 of 5-FU, and 30 mg/body of dl-LV for 5 consecutive days and arm B was 300 mg/m2 of 5-FU and 30 mg/body of dl-LV for 5 consecutive days. Both regimens were followed by biweekly administration of the same dose of dl-LV and 5-FU in outpatients. Arm A was started at the 26th postoperative day and arm B at the 21st day on average. Some 26 cases composed of 11 cases of arm A and 15 cases of arm B completed the administration schedules. Only one case in arm A was complicated by local recurrence around 35 months after operation. Major toxicities were anorexia and neutropenia. Both toxicities were seen more in arm A than in arm B, showing complete recovery in all cases. These data suggest that PFL-therapy and FL-therapy seem to be possible and promising surgical adjuvant therapies for advanced colorectal carcinoma.

Topics: Adenocarcinoma; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neutropenia; Rectal Neoplasms; Survival Rate

We undertook a randomized trial in patients with advanced colorectal cancer, comparing 5-fluorouracil and leucovorin versus combination of these agents with additional cisplatin. Between July 1991 and October 1994, 21 patients with advanced measurable colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either 5-FU (500-750 mg/body) and LV (30 mg/body) for 5 days, or the combination of 5-FU and LV in the same daily dose plus cisplatin (10 mg/body). The overall responses were 30% and 36.3% for the 5-FU/LV and the 5-FU/LV/CDDP treatment arms, respectively. The three-drug combination appeared superior to 5-FU/LV for response duration. A comparative analysis of the toxicities experienced by the patients in the two treatment groups showed a comparable rate, although moderate leukocytopenia was prolonged in one patient treated with 5-FU/LV for 5 days. We conclude that the 5-FU/LV/CDDP treatment arm is an effective therapy for advanced colorectal cancer, but further attempts should be made to increase response rate, prolong response duration and assure effective therapy.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Pilot Projects; Vomiting

A multicentral cooperative study was conducted to evaluate the clinical efficacy and toxicity of l-Leucovorin (l-LV) and 5-fluorouracil (5-FU) in advanced colorectal cancer. The administration schedule was a two-hour intravenous infusion of l-LV (250 mg/m2) and an intravenous bolus injection of 5-FU (600 mg/m2), given one hour after the beginning of the l-LV infusion. Sixty-four patients were treated weekly for six weeks followed by two-weeks rest, and then evaluated for response. Complete response and partial response were obtained in 21 patients (32.8%). The median survival time was 12.8 months. The most prominent side effects were anorexia (57.8%), nausea and vomiting (56.3%), diarrhea (48.4%) and myelosuppression such as leucopenia (54.7%), thrombocytopenia (18.8%) and decreased hemoglobin (40.6%). These side effects, however, were within permissible levels. Severe toxicity was prevented by discontinuance of the treatment. From the present study, l-LV and 5-FU combination therapy seems to be a very promising and useful treatment for patients with advanced colorectal carcinoma.

Topics: Adult; Aged; Anorexia; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Remission Induction; Survival Rate

Topics: Adenocarcinoma; Aged; Anorexia; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Prognosis

Thirty patients with a diagnosis of metastatic adenocarcinoma of the lung were entered on a trial to evaluate the antitumor efficacy of 5-fluorouracil 370 mg/m2 daily for 5 days every four weeks in combination with folinic acid 200 mg/m2, 60 min prior to 5FU. All patients had a good performance status, bidimensionally measurable disease, and weight loss less than or equal to 5% of preillness weight. Of the 29 evaluable patients, only two (7%) had partial responses (95% confidence limits 1-24%). Eleven (38%) had stable disease and 16 (55%) progressed. The two responding patients survived 12 and 60+ weeks. The median survival of all evaluable patients was 25 weeks (range 7-60+) and that of the stable patients was 26 weeks. The principal toxicities observed were diarrhea and stomatitis. Myelosuppression was rarely dose limiting. In contrast to the results of treatment with 5FU and folinic acid in metastatic colorectal cancer and breast cancer, the results of treatment with this combination of agents have been much less encouraging in adenocarcinoma of the lung.

Topics: Adenocarcinoma; Adult; Aged; Allopurinol; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Fatigue; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Nausea; Nervous System; Stomatitis

FOLFIRINOX (FFX, a combination of oxaliplatin, irinotecan, fluorouracil, and leucovorin) and gemcitabine plus nab-paclitaxel (GnP) have been used as standard, first-line treatments for advanced pancreatic cancer. However, no study has compared the efficacy of the 2 regimens. This study retrospectively compared the efficacy and safety of the 2 regimens in patients with locally advanced pancreatic cancer.. We reviewed the records of patients with locally advanced pancreatic cancer who started FFX or GnP as first-line chemotherapy as part of a multicenter retrospective study in patients with unresectable pancreatic cancer treated with FFX or GnP (NAPOLEON study).. Sixteen of the 63 patients were treated with FFX, and the other 47 patients were treated with GnP between December 2013 and March 2017. There were no significant differences in median overall survival rate between the GnP (15.5 months) and FFX (14.3 months, P = 0.60) groups or median progression-free survival rate between the GnP (8.8 months) and FFX (8.1 months, P = 0.51) groups. Both treatments were generally well tolerated, although anorexia was more severe in the FFX group than in the GnP group.. The effects of FFX and GnP were similar but resulted in different toxicities, which could guide agent choice.

Topics: Adult; Aged; Albumins; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Diarrhea; Female; Fluorouracil; Gemcitabine; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neutropenia; Outcome Assessment, Health Care; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Retrospective Studies

Data on FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer are limited. In the JASPAC06 study-a nationwide, multicenter, observational study-FOLFIRINOX for patients with unresectable or recurrent pancreatic cancer as any line of treatment showed favorable efficacy and safety in Japanese clinical practice.. We performed exploratory analyses of patients with unresectable or recurrent pancreatic cancer who received FOLFIRINOX as the second-line chemotherapy in Japanese clinical settings.. Of the 399 evaluable patients, 44 were eligible for inclusion in the analysis. The patients' characteristics were as follows: median age, 62 years; men, 26 (59%); Eastern Cooperative Oncology Group-Performance status 0/1, 30 (68%)/14 (32%); disease status, recurrent/local/metastatic: 4 (9%)/8 (18%)/32 (73%). The initial dose was reduced in 28 (64%) patients. The median time to treatment failure and number of cycles were 4.5 (range, 0.2-19.1) months and 6 cycles (range, 1-13 or more), respectively. The major grade 3/4 adverse events were neutropenia in 29 (66%), leucopenia in 17 (39%), anorexia in 7 (16%), febrile neutropenia in 5 (11%), and anemia in 5 (11%) patients. The median overall survival, progression-free survival, and 1-year survival rates were 10.3 (95% confidence interval [CI], 7.2-13.3), 4.1 (95% CI, 2.6-5.5) months, and 30%, respectively.. Our findings suggest that FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer was effective in patients with a good performance status. It displayed toxicity similar to that observed with its use as a first-line treatment.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Glucuronosyltransferase; Humans; Irinotecan; Japan; Kaplan-Meier Estimate; Leucovorin; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxaliplatin; Pancreatic Neoplasms; Progression-Free Survival; Survival Analysis; Treatment Outcome

Limited literature on the role of intraarterial chemotherapy as first-line therapy for penile squamous cell carcinoma is available.. From 2005 to 2013, a total of 12 patients with various stages of penile squamous cell carcinoma received intraarterial chemotherapy. The chemotherapeutic agents used were methotrexate, mitomycin C, bleomycin, cisplatin, and 5-fluorouracil. Surgery was followed by the tumour responses.. An objective tumour response was noted in 10 of 12 patients (83%, 4 complete responders and 6 partial responders). In node-negative patients (n=7), the response rate was 100% (4 complete responders and 3 partial responders). Even in advanced penile squamous cell carcinoma with nodal invasion, a response rate of 60% could be achieved. Grade 2 anorexia was the most frequent chemotherapy-related toxicity and no toxic death was noted. Recurrence-free survival was significantly better in patients without lymph node invasion (log-rank test, P=0.041).. Neoadjuvant intraarterial chemotherapy displayed excellent responses for penile squamous cell carcinoma. This therapy could effectively shrink the tumour burden or even achieve complete response before surgery. It could be used as first-line strategy for penile cancer treatment because of low toxicity.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Fluorouracil; Humans; Infusions, Intra-Arterial; Inguinal Canal; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Mitomycin; Neoadjuvant Therapy; Penile Neoplasms; Retrospective Studies

NSABP C-06 study showed that an oralUFT /Leucovorin(LV)regimen proved to be equivalent to an infusional 5-fluorouracil/LV regimen in an adjuvant setting for colorectalcancer. Thus, the oralregimen has been approved as the treatment of choice in Japan, but compliance of the regimen for Japanese patients has scarcely been reported. We assessed the compliance of oralUFT /LV adjuvant chemotherapy(5 cycles, 25weeks)in 99 consecutive colorectal cancer patients undergoing curative resection. Eighty-two percent(81 of 99)received all scheduled doses of UFT plus LV for five cycles. The mean relative dose intensity was 0. 87. Mean treatment courses given were 4. 5. The treatment was discontinued because of toxicity in 18 of the 99 patients. Nine of 18 received UFT only after the toxicities resolved. The remaining nine patients had no chemotherapy. The toxicity was generally mild. Six patients each had grade 3 diarrhea or anorexia, despite inclusion of overlapping cases. Fifteen of the 99 patients(15%)developed grade 3 toxicities. These results suggest that the compliance of oral UFT/LV treatment was equivalent to that of oral UFT adjuvant treatment for various cancers(80-90%).

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colorectal Neoplasms; Diarrhea; Female; Humans; Leucovorin; Male; Middle Aged; Tegafur; Uracil

We evaluated the efficacy and safety of modified FOLFIRI for patients with refractory advanced or recurrent colorectal cancer. Modified FOLFIRI was given 29 patients (21 men and 8 women, with a median age of 61.0 years) from 2 to 16 times (median 10.0). 19 out of 29 patients were colon cancer, and the other 10 were rectal cancer. 18 patients were administered as first-line chemotherapy, and 11 were more than second line. CPT-11 was administered at a dose of under 150 mg/m(2), to remain within the limits in Japan. The response to treatment was CR in 3 patients, PR in 8, and SD in 12. The response rate was 37.9%. Grade 4 hematologic toxicities included leukocytopenia in 2 patients, neutropenia in 7 and anemia in 1. Grade 3/4 non-hematologic toxicities included febrile neutropenia in 4 patients, anorexia in 3, fatigue in 3, and nausea, diarrhea and interstitial pneumonia in 1. Except in 2 patients, all reactions could be controlled with the use of G-CSF or by setting drug holiday. In summary, modified FOLFIRI is a safe and effective regimen even at a dose of under 150 mg/m(2), of CPT-11. It can be given with good tolerance for patients with refractory advanced or recurrent colorectal cancer on an outpatient basis with due care especially for neutropenia.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Administration Schedule; Feasibility Studies; Female; Fluorouracil; Humans; Infusion Pumps, Implantable; Infusions, Intravenous; Irinotecan; Leucovorin; Leukopenia; Male; Middle Aged; Neutropenia; Quality of Life; Rectal Neoplasms

FOLFOX regimens were administered to 14 patients with unresectable advanced or recurrent colorectal cancer from 1 to 9 cycles (median 5 cycles). In our patient characteristics, 10 patients had previous chemotherapies, 3 patients showed performance status 3. The response rate was 21%, and median time to progression was 5.0 months. Frequency of grade 3/4 adverse effect was 57% in neutropenia, 36% in leucopenia, 36% in thrombocytopenia, and 7% in allergic reaction. Only 64% patients could complete the treatment, for these adverse events brought treatment failure at 3-6 cycles. Median relative dose-intensity was 80-90% during 1-4 cycles, but about 50% after 5 cycles for these adverse events. No patient had grade 3 neurologic toxicity,because no one was administered over 10 cycles. FOLFOX regimens showed good anti-tumor effects but poor tolerability after 5-6 cycles in our patients.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Organoplatinum Compounds

Oxaliplatin (L-OHP) was administered to 10 patients previously treated for refractory advanced or recurrent colorectal cancer. The number of times each had received previous chemotherapy treatment ranged from 1 to 5 (median 3) for durations of 2.5 to 52.8 (median 11.7) months. At the time, L-OHP was not yet approved for sale in Japan, and could only be imported from overseas for personal use. As this made it very expensive,we used a low L-OHP dose of 100 mg/body. Combinations with 5-FU were administered differently from previous regimens; these included chronotherapy, weekly high-dose, FOLFOX 4, and FOLFOX 6. L-OHP was administered from 1 to 14 times (median 4.5), and the response to treatment was PR in 2 patients and NC in 5. The response rate was 22.2%. Although in NC there was a tendency toward tumor reduction in 2 of the 5 patients, the treatment had to be suspended because of their financial situations. Overall survival from commencement of the first treatment was 3.1 to 58.7 months (median 17.6+) and after starting L-OHP was 0.6 to 17.2 months (median 6.4+). Adverse events included bone marrow suppression in three patients, 3 cases of leukocytopenia (grade 3 in two patients and grade 4 in one), grade 4 thrombocytopenia in one patient,grade 3 sensory disturbance in one patient,and grade 3 anorexia in two patients. All reactions were able to be controlled except for one patient with Grade 4 thrombocytopenia. In summary,treatment with L-OHP as salvage chemotherapy can possibly contribute to prolongation of survival time in cases of refractory advanced colorectal cancer. It is useful to combine L-OHP with high-dose continuous administration of 5-FU,namely FOLFOX regimens.FOLFOX 6 is the most useful of the FOLFOX regimens because it is simple and can be administered on an outpatient basis.

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Salvage Therapy; Thrombocytopenia

A clinical study has been conducted to investigate whether chemotherapy with 24 hour infusion of CPT-11/oral UFT/LV is an effective and safe regimen for advanced or recurrent colorectal cancer. The chemotherapy consisted of a fixed dose of UFT (300 mg/m(2)/day)/LV (75 mg/body) orally administered daily (day 1-day 21) followed by CPT-11 (80-120 mg/m(2)) iv, as a 24-hour infusion (day 1 and day 15). This treatment was carried out weekly for 3 weeks followed by a week rest period, then repeated every 4 weeks. The MTD was reached at 120 mg/m(2) of CPT-11 (2 cases of grade 3 leucopenia and neutropenia) and 100 mg/m(2) (a case of grade 3 anorexia). Therefore the 100 mg/m(2) dose level was established as the recommended dose (RD). All patients were evaluable for efficacy; 5 PR, 4 SD and 1 PD. The overall response rate was 41.7%. The present study suggests that combination chemotherapy with CPT-11 and oral UFT/LV is well tolerated and might be a promising regimen for advanced or recurrent colorectal cancer.

Topics: Administration, Oral; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intravenous; Irinotecan; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Nausea; Neutropenia; Tegafur; Uracil

The uracil/tegafur (UFT) plus oral Leucovorin (LV) regimen is one of the standard chemotherapy modalities for colorectal cancer, and has been reported to have fewer side effects. In this study, we investigated the efficacy and toxicity of UFT/LV regimen in elderly patients.. The subjects were twelve patients older than 70 years (median age, 76 years), who received a UFT/LV regimen for colorectal cancer between January 2004 and June 2005. Chemotherapy was attempted for metastatic colorectal cancer in seven patients and for postoperative adjuvant chemotherapy in five patients. The response rate and toxicity were compared with those of patients younger than 70 years old.. Four courses of chemotherapy, in median, were delivered. The regimen consisting of UFT 300 mg/m(2) was completed in all patients. One patient achieved a complete response and another patient a partial response, thus resulting in an overall response rate of 28.6%. Three patients experienced Grade 1 diarrhea, and seven patients had Grade 1 or 2 anemia. Grade 3 or 4 toxicity was not recognized in all patients.. Treatment with UFT/LV regimen is effective and well tolerated in elderly as well as younger patients.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Combined Modality Therapy; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Leucovorin; Male; Middle Aged; Remission Induction; Tegafur; Uracil

In Japan, cancer chemotherapy for advanced and recurrent colorectal cancer has not been adequately developed in comparison with the USA and Europe. However, the number of patients with advanced colorectal cancer has increased dramatically in this decade. Therefore, effective and feasible regimens against colorectal cancer are urgently needed. We designed a new regimen to evaluate the efficacy and feasibility of weekly low dose CPT-11 combined with 5-FU/l-LV therapy based on an RPMI regimen against advanced and recurrent colorectal cancer. Twenty patients were enrolled in this study. Weekly administration (CPT-11; 60 mg/m(2) div for 1st-line chemotherapy, 40 mg/m(2) div for 2nd-or 3rd-line chemotherapy, l-LV; 200 mg/m(2) div, 5-FU; 500 mg/m(2) iv, 3 consecutive weeks, 1-week break) was performed on an ambulatory basis. The treatment cycles were repeated every 4 weeks until disease progression and/or severe toxic events occurred. The overall response rate was 31.6% with 5.3% complete response and 26.3% partial response in addition to 42.1% with no changes beyond 3 months. These results suggested that the clinical benefit was shown in 73.7% of patients. Furthermore, median TTF (time to failure) of this regimen was 6.5 months and MST was 20.4 months, respectively. On the other hand, adverse events were restricted to grade 3 with 30.0% neutorocytopenia and 5.0% thrombocytopenia. Therefore, weekly low-dose CPT-11 combined with 5-FU/l-LV therapy seems to be extremely useful, with excellent anti-tumor effect and tolerable adverse reactions, for the treatment of advanced and recurrent colorectal cancer on an ambulatory basis.

Topics: Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Irinotecan; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Quality of Life; Rectal Neoplasms

We report the effects and toxicities of intravenous administration of cisplatin, 5-FU and high-dose leucovorin for advanced esophageal cancer. Eight patients were registered and sixteen lesions were measurable. Of these sixteen lesions, thirteen were primary or synchronous metastatic lesions, and the response was 69%. Three were recurrence lesions, and the response rate for them was 0%. Including seven neoadjuvant cases, ten patients had oral mucositis, and seven patients had appetite loss. Other toxicities were diarrhea, myelosuppression, renal dysfunction, and alopecia. All were reversible after administration. It is suggested that this treatment regimen is a superior neoadjuvant chemotherapy with low toxicity.

Topics: Aged; Aged, 80 and over; Alopecia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local

Most nonendocrine pancreatic neoplasms are adenocarcinomas of ductal cell or acinar origin. Primary carcinomas of the pancreas with squamous differentiation are rare enough to warrant a search for other primary tumors. In the past few decades, well-documented individual reports and large series reviews support the view that these squamous neoplasms are indeed of pancreatic origin and not uncommonly exhibit cystic degeneration. Late manifestation and unfavorable prognosis seem to be uniform features. We report a case with many of these features.

Topics: Abdominal Pain; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Carcinoma, Squamous Cell; Cholangiopancreatography, Endoscopic Retrograde; Deoxycytidine; Fluorouracil; Gemcitabine; Humans; Jaundice; Leucovorin; Liver Neoplasms; Male; Middle Aged; Pancreatic Cyst; Pancreatic Neoplasms; Tomography, X-Ray Computed

Topics: Administration, Oral; Adolescent; Amphotericin B; Anorexia; Blood Platelets; Blood Transfusion; Candidiasis; Drug Eruptions; Humans; Infusions, Parenteral; Injections, Intramuscular; Leucovorin; Methotrexate; Nausea; Osteosarcoma; Pneumothorax; Stomatitis; Vomiting