levoleucovorin and Abdominal-Neoplasms

5-fluorouracil remains the standard therapy for patients with advanced/metastatic colorectal cancer. Pre-clinical studies have demonstrated the biological modulation of 5-fluorouracil by methotrexate and leucovorin. This phase II study was initiated to determine the activity and toxicity of sequential methotrexate--leucovorin and 5-fluorouracil chemotherapy in patients with advanced colorectal cancer.. Ninety-seven patients with metastatic colorectal cancer were enrolled onto the study. Methotrexate--30 mg/m2 was administered every 6 hours for 6 doses followed by a 2 hour infusion of LV--500 mg/m2. Midway through the leucovorin infusion, patients received 5-fluorouracil--600 mg/m2. This constituted a cycle of therapy and was repeated every 2 weeks until progression.. The median age was 64 yrs (34-84) and the Eastern Cooperative Group Oncology performance score was 0 in 37%, 1 in 55% and 2 in 8% of patients. Partial and complete responses were seen in 31% of patients with a median duration of response of 6.4 months. The overall median survival was 13.0 months. The estimated 1-year survival was 53.7%. Grade III and IV toxic effects were modest and included mucositis, nausea and vomiting.. This phase II study supports previously reported data demonstrating the modest clinical benefit of 5-FU modulation utilizing methotrexate and leucovorin in patients with metastatic colorectal cancer. Ongoing studies evaluating 5-fluorouracil modulation with more novel agents (Irinotecan and/or oxaliplatin) are in progress and may prove encouraging.

Topics: Abdominal Neoplasms; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Routes; Drug Synergism; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Survival Rate; Treatment Outcome

In a preceding study, we established the tolerance and pharmacokinetic behavior of 5-fluoro-2'-deoxyuridine (FdUrd) given by the intraperitoneal (IP) route. A dose of 3 g daily x 3 days was found satisfactory for Phase II study and exploration of biochemical modulation. Therefore, the current study was conducted to study the tolerance and pharmacokinetics of such a dose-schedule and route of FdUrd combined with escalating doses of leucovorin (LV). Fourteen patients were entered and 13 were evaluable for tolerance determination. Pharmacologic determinations of IP FdUrd and 5-Fluorouracil (FUra) derived from it and LV were obtained by HPLC methods on 11 occasions. Findings were compared with the preceding study of FdUrd alone. LV did not appear to alter the tolerance of IP FdUrd even in the four patients receiving the highest dose of LV (640 mg). Toxicities included nausea, vomiting, and rarely neutropenia and diarrhea. Pharmacokinetic parameters indicate a parallel rate of egress of FdUrd and LV from the peritoneal cavity. The pharmacologic advantage for FdUrd is at least 3 logs as previously reported and one log for LV. Evidence of antitumor effect was noted particularly among untreated patients with gastrointestinal primaries. We conclude that IP FdUrd 3 g and LV in doses of up to 640 mg x 3 days are well tolerated. Since FdUrd is more potent, has an even greater hepatic clearance and shows greater potential for modulation with LV than FUra, it may be the preferred fluoropyrimidine for subsequent studies via the IP route in the treatment of carcinomas with prominent peritoneal spread. The pharmacologic advantage for leucovorin is limited but it is a good marker for peritoneal clearance since it parallels FdUrd clearance.

Topics: Abdominal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Floxuridine; Half-Life; Humans; Infusions, Parenteral; Leucovorin; Male; Metabolic Clearance Rate; Peritoneal Neoplasms

Seventy-three patients with Stage III abdominal non-Hodgkin's lymphoma were prospectively treated following two sequential protocols (P): L278 P (group A, 33 patients) (1978-1983) and L384 P (group B, 40 patients), (1984-1991). No patient received radiotherapy. The L278 P included 7 drugs: cyclophosphamide, vincristine (VCR), adriamycin (ADR), prednisone, methotrexate (MTX), dexamethasone, and 6-mercaptopurine, given for remission induction, maintenance, and CNS prophylaxis. In the L384 P we introduced a consolidation phase consisting of intravenous MTX and citrovorum factor rescue, and IV cytosine arabinoside. VCR was also added to the monthly doses and the maintenance phase was reduced from 18 to 15 months. From January 1988 we changed ADR for epirubicin in the same doses. Prophylactic treatment of the CNS, in the L384 P, was intensified by increasing the number of doses of MTX IT in the remission, induction, and consolidation phases, and with the use of ara-C IT. Laparotomy in 50 patients allowed partial resection in 16, and second-look laparotomy was performed in 27 patients. Viable tumor was found in four patients. Three patients (G-A) died from metabolic complications and another 4 (2 G-A and 2 G-B) failed to attain CR and died. A total of 28 (85%) of 33 children of G-A and 38 (95%) of 40 children in G-B achieved CR. Five children died in remission (2 G-A, 3 G-B). Three patients (G-A) relapsed in the CNS and one (G-B) relapsed in the abdomen and died. Disease-free survival at 120 months was 70% in G-A and 84% in G-B.

Topics: Abdominal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Child; Child, Preschool; Costa Rica; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Female; Humans; Infusions, Intravenous; Leucovorin; Life Tables; Lymphatic Metastasis; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Neoplasm Recurrence, Local; Prednisone; Prospective Studies; Remission Induction; Survival Rate; Vincristine

Thirteen patients with intra-abdominal malignancies entered a phase I study of fluorouracil (5-FU) given by continuous infusion (96 h) iv and ip, simultaneously, and modulated by high-dose folinic acid-iv. Severe but reversible stomatitis was the only dose-limiting toxicity at a dose of 5-FU of 550 mg/m2/day. Local toxicity (5-FU-induced abdominal pain) was a significant side effect in patients receiving more than 1 cycle. The pharmacokinetic advantage of 5-FU-ip was confirmed in our study (ratio AUC peritoneum/plasma between 160 and 328). The systemic exposure to 5-FU (plasmatic AUC ranging from 73.4 to 173.21 microM) and to AF were found in efficacious ranges. The recommended dose of 5-FU iv and ip is 500 mg/m2/day. This regimen is feasible and may potentially have application for adjuvant chemotherapeutic programs after surgery for colorectal cancer.

Topics: Abdominal Neoplasms; Drug Synergism; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intraperitoneal; Leucovorin; Male; Middle Aged; Neoplasms

An 82-year-old man underwent anterior resection for rectal cancer in 2006. Local recurrence was diagnosed 5 years and 4 months after the operation. He could not undergo intensive chemotherapy because of his age and health status(a history of tubercular and pancytopenia due to chronic hepatitis C). sLV5FU2 chemotherapy was initiated. The CEA level decreased immediately after chemotherapy, and a complete response was observed on CT. After 18 courses, chemotherapy was discontinued. A complete response was detected for 1 year after the chemotherapy holiday began. For patients who experience difficulty tolerating intensive chemotherapy, good outcomes have been achieved even if relatively light regimens are used. For elderly patients or those with several complications, we suggest selecting a regimen based on the QOL.

Topics: Abdominal Neoplasms; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Male; Rectal Neoplasms; Recurrence; Treatment Outcome

For patients with HER2-overexpressing gastric cancer, there is an improved prognosis with additional trastuzumab to chemotherapy with a platinum compound and a fluoropyrimidin in first-line therapy. Second-line combinations are currently evaluated in various studies.. We report the case of a 43-year-old male patient who came to our hospital with recurrent metastatic gastric cancer after curative surgery 18 months before. His disease responded well to several therapeutic regimens. Firstline chemotherapy with a combination of epirubicin, oxaliplatin and capecitabine (EOX) and the following therapies -- peritonectomy, multivisceral resection, hyperthermic intraperitoneal chemotherapy (HIPEC), and secondline chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin (FLO) - induced a complete remission. At the time of the subsequent progression, HER2 overexpression was detected. We administered the combination of irinotecan, 5-fluorouracil, leucovorin (FOLFIRI) and trastuzumab, which to our knowledge was used for the first time in a patient with metastatic gastric cancer in third-line therapy. This regimen again induced a complete remission of the disease, which has been sustained now for at least 8 months.. This is the first time in the literature that a combination of FOLFIRI and trastuzumab (FOLFIRIT) was used successfully in a patient with recurrent metastatic gastric cancer.

Topics: Abdominal Neoplasms; Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease Progression; Fluorouracil; Gastrectomy; Gene Expression Regulation, Neoplastic; Humans; Leucovorin; Lymph Node Excision; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Palliative Care; Receptor, ErbB-2; Reoperation; Stomach Neoplasms; Tomography, X-Ray Computed; Trastuzumab; Ultrasonography

Topics: Abdominal Neoplasms; Aged; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Fibromatosis, Aggressive; Fluorouracil; Gemcitabine; Humans; Leucovorin; Male; Treatment Outcome

The detection of gastrointestinal signet-ring cell carcinoma by endoscopy can be a diagnostic challenge. The main clinical features include atypical metastasis and a poor prognosis. We present a case of a metastasizing signet-ring cell carcinoma with unknown primary location arising in 71-year-old female. Following 6 cycles of a routine intravenous FU/FA chemotherapy, an almost complete remission could be observed. After 2 years of follow up, metastatic recurrence was detected to the lower back musculature. This case report emphasizes the difficulties in diagnosing signet-ring cell carcinoma by endoscopy and demonstrates an unusual clinical course.

Topics: Abdominal Neoplasms; Aged; Back; Biopsy, Needle; Carcinoma, Signet Ring Cell; Diagnosis, Differential; Endoscopy, Gastrointestinal; Female; Fluorouracil; Humans; Leucovorin; Magnetic Resonance Imaging; Muscle Neoplasms; Muscle, Skeletal; Neoplasms, Unknown Primary; Tomography, X-Ray Computed

The aim of this study was to analyse the effect of LMB-89 protocol and surgical procedure at initial laparotomy on the outcome in children with abdominal B-cell NHL. The initial surgery intervention was: complete resection (20% pts), subtotal resection (20%), partial resection (4%), biopsy (36%). Postoperative complications occurred in 5 children. Complete recovery (CR) was achieved in 92% pts. There were 4% non responder patients. Two patients died before CR evaluation (tumour lysis syndrome; bleeding and multi organ failure after initial surgery). One patient died in CCR from sepsis probably influenced by the previous local operation. 10.8% patients relapsed. The estimate EFS for all patients with AB-NHL is 81%, 85% for stage III and 73% for stage IV. Major surgery in advanced stages is not recommended since it delays chemotherapy and fails to improve overall survival.

Topics: Abdominal Neoplasms; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Humans; Hydrocortisone; Infant; Laparotomy; Leucovorin; Lymphoma, B-Cell; Male; Methotrexate; Prednisone; Risk Factors; Time Factors; Treatment Outcome; Vincristine

A 21-year-old female presenting with malignant histiocytosis was initially treated with conventional aggressive chemotherapy resulting in complete remission (CR) but relapsed within 6 months of discontinuation. The patient was reinduced with two cycles of cis-platinum, cytosine arabinoside and mitoxantrone and achieved CR, at which time she received single agent high-dose melphalan followed by autologous bone marrow transplant. She remains in CR 36 months after the autograft procedure.

Topics: Abdominal Neoplasms; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Female; Histiocytic Sarcoma; Humans; Leucovorin; Methotrexate; Mitoxantrone; Remission Induction; Transplantation, Autologous; Vincristine

Many patients with gastrointestinal (GI) tumors develop extensive peritoneal and serosal metastasis and/or malignant ascites which respond poorly to available treatments. Twelve patients with tumors confined primarily to the intraabdominal cavity were treated with intraperitoneal (IP) 5-fluorouracil (5-FU) in escalating concentrations (2 to 4 mmol/L) in combination with leucovorin (dl-5-formyltetrahydrofolic acid or folinic acid; dl-CF) in a 2-L volume, either by eight consecutive four-hour dwells or once daily for five days. CF dose was 20.8 or 104 mumol/L. Nine of the patients had pancreatic carcinoma, one had stomach carcinoma, and two had hepatobiliary neoplasms. Median age was 62.5 years and median Eastern Cooperative Oncology Group (ECOG) performance status was 3. Toxicity included mucositis, diarrhea, nausea and vomiting, leucopenia, skin rash, and abdominal pain, and was similar to that previously reported for IP 5-FU used as a single agent. Four episodes of peritonitis occurred, but all patients responded to antibiotics. At the 20.8 mumol/L dose, dl-CF concentration in the peritoneal fluid declined from 10.4 +/- 3.0 3.0 mumol/L at one hour to 4.9 +/- 2.2 mumol/L at four hours, corresponding to a mean absorption half-life of 127 +/- 49 minutes and a mean peritoneal clearance of 13.0 +/- 4.5 mL/min. Decline was biphasic in all but five of the 19 exchanges evaluated. The levels of l-CF (biologically active isomer of dl-CF) were 2.8 +/- 2.5 mumol/L after 60 minutes and 1.2 +/- 0.7 mumol/L after four hours. The peritoneal area under the concentration v time curve (AUC) for 5-FU increased proportionally with dose. For example, the AUC at 2.0 and 3.5 mmol/L was 129 +/- 25 and 201 +/- 23 mmol/L X minute, respectively. However, the maximal peritoneal to plasma AUC ratio was 461 at the 2 mmol/L dose, but decreased with increasing doses as systemic clearance decreased. This regimen was well tolerated in patients with advanced cancer, but must be evaluated further to determine its clinical efficacy.

Topics: Abdominal Neoplasms; Adult; Antineoplastic Combined Chemotherapy Protocols; Catheterization; Drug Evaluation; Female; Fluorouracil; Humans; Injections, Intraperitoneal; Kinetics; Leucovorin; Male; Middle Aged; Peritoneum; Peritonitis