levoleucovorin and Hepatitis-B

We analyzed the results of the LMB-89 protocol performed in seven centers in Venezuela in 96 children having B-cell non-Hodgkin lymphoma treated from 1995 to 2002.. Mean age was 7.1 years with 71 (74%) been male. Eighty-two patients (85%) had diffuse small cell lymphoma Burkitt and Burkitt-like, and 14 (15%) had diffuse large B-cell lymphoma. Initial disease sites included the abdomen in 67%, peripheral nodes in 8%, and mediastinal in 4%. Treatment was directed to risk groups as described for LMB-89 protocol. Group A: seven patients (7%), group B: 80 patients (83%), and group C: nine patients (9%).. Mean follow-up was 35 +/- 31 months. Complete remission (CR) occurred in 70 patients (73%); four patients (6%) had relapse during the first year and ten patients (10%) had progressive disease. Overall survival (OS) and event free survival (EFS) were 85 and 80% at 1 year, and 82 and 75% at 2 years, respectively. The EFS by therapeutic groups at 3 years was A: 100%; B: 76%, and C: 56%.. neutropenia in 75%, thrombocytopenia in 63%, febrile neutropenia in 39%. Viral infections: hepatitis B in 20%, hepatitis C in 2%, and Herpes zoster in 3%. Tumor lysis syndrome (TLS) occurred in 9% during induction phase with a high mortality of 44% (urate-oxidase was available only at the end of the study).. The high mortality rate during induction phase prohibited a better EFS. Prophylactic use of xantine-oxidase may improve future results. The high incidence of hepatitis B requires a vaccination program.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Cytarabine; Disease Progression; Disease-Free Survival; Doxorubicin; Etoposide; Female; Hepatitis B; Hepatitis B Vaccines; Humans; Hydrocortisone; Leucovorin; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Male; Methotrexate; Prednisone; Recurrence; Treatment Outcome; Venezuela; Vincristine

To conduct a pilot trial of hepatic arterial infusion (HAI) of floxuridine (FUDR), leucovorin, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (FLAP) in nonresectable hepatocellular cancer (HCC) confined to the liver and assess the effects of hepatitis B (HBV) and hepatitis C (HCV) viral markers on toxicity, response to treatment, and patient survival.. Of 31 HCC patients, 13 were HBV- and HCV-nonreactive, and 18 had evidence of either current or prior HBV and/or HCV infection. Treatment was delivered through percutaneous hepatic arterial catheters, and Infusaid pumps (Shiley Infusaid, Norwood, MA) were placed in responding patients. Cisplatin (100 mg/m2) and Adriamycin (30 to 35 mg/m2) were administered on day 1, followed by a continuous 24-hour HAI of an admixture of floxuridine (60 mg/m2) and leucovorin (15 mg/m2) daily for 4 days. Treatment was repeated every 5 weeks.. Twelve (41%) of 29 assessable patients had a partial response (PR), with a median time to disease progression of 13 months. Six (50%) of 12 HBV-negative (HBV-)/HCV-negative (HCV-) and six of 17 (35%) HBV-positive (HCV+) and/or HCV-positive (HCV+) patients achieved a PR. Eight patients have been maintained in remission for a median duration greater than 15.5 months. The median survival duration of all 31 patients was 15 months, 7.5 months among HBV+ and/or HCV+ patients, and significantly longer among hepatitis-non-reactive patients (P = .007). (A median has not yet been reached.) Granulocylopenia (< 0.1 x 10(3)/microL), thrombocytopenia (< 25 x 10(3)/microL), and hospitalizations for infectious complications were significantly more common among HBV-HCV-reactive than -nonreactive patients: 56%, 50%, and 67% versus 15%, 15%, and 8%, respectively (P < .05 for all).. HAI of FLAP has induced long-term PR and has palliated extensive nonresectable HCC. Positive hepatitis serology appeared to increase bone marrow susceptibility to myelotoxic drugs. Conceivably, one or both viruses may have a direct inhibitory effect on bone marrow progenitors and thereby contribute to the observed myelotoxicity.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cisplatin; Doxorubicin; Female; Floxuridine; Hepatic Artery; Hepatitis B; Hepatitis C; Humans; Infusion Pumps; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Middle Aged; Pilot Projects; Survival Rate

Reactivation of hepatitis B virus (HBV) has recently been reported as a fatal complication in patients undergoing cytotoxic chemotherapy. We herein describe a case of reactivation in a 76-year-old man who had undergone pelvic exenteration for colorectal cancer (CRC). He was treated with a modified FOLFOX6 chemotherapy regimen after the operation. Thirteen months later, his laboratory data showed severe liver dysfunction. His hepatitis B surface antigen (HBsAg) test was positive, and his HBV-DNA level was elevated. We diagnosed the patient with HBV reactivation as his HBsAg test was negative before starting chemotherapy. His liver dysfunction improved after administration of entecavir. This is the first report describing HBV reactivation following chemotherapy for an HBsAg-negative CRC patient.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Colorectal Neoplasms; Fluorouracil; Guanine; Hepatitis B; Hepatitis B Surface Antigens; Humans; Leucovorin; Male; Organoplatinum Compounds; Treatment Outcome; Virus Activation

Hepatitis Bvirus (HBV)reactivation induced by cancer chemotherapy is increasingly being observed. However, most reports of resolved HBV[hepatitis Bsurface antigen(HBs-Ag)negative and hepatitis Bsurface antibody(HBs-Ab)positive and/or hepatitis Bcore antibody(HBc-Ab)positive]infection involve patients with hematological malignancies, whereas few describe patients with solid cancers. In this study, we report our experience with a patient with resolved HBV infection who was undergoing bevacizumab plus FOLFIRI treatment for rectal cancer when HBV reactivation was noted. This 74-year-old man was HBs-Ag negative, HBs-Ab negative, HBcAb positive, hepatitis B e antigen(HBe-Ag)negative, and hepatitis Be antibody(HBe-Ab)negative and had HBV-DNA levels below the detection limit. Forty-two days after the 21st cycle of bevacizumab plus FOLFIRI treatment, his aspartate aminotransferase and alanine aminotransferase levels increased. At followup examination, he was HBs-Ag positive, HBs-Ab negative, HBc-Ab positive, HBe-Ag positive, and HBe-Ab positive, while his HBV-DNA levels had increased to>9.0 log copies/mL, confirming HBV reactivation. His treatment included entecavir(0.5mg/ day)administration and plasmapheresis, but he succumbed to liver failure 82 days after his final dose of bevacizumab plus FOLFIRI. Thus, HBV reactivation can occur during bevacizumab plus FOLFIRI treatment in rectal cancer patients with a resolved prior HBV infection. No similar report has been published to date, and we believe that this study will be important when discussing HBV reactivation in patients with resolved HBV infection. Future studies will require detailed investigations in a larger number of institutions.

Topics: Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Fluorouracil; Hepatitis B; Hepatitis B virus; Humans; Leucovorin; Male; Rectal Neoplasms; Virus Activation

We describe nine asymptomatic chronic carriers of hepatitis B virus, four males and five females, with a mean age of forty-six years and all were Chinese, who developed exacerbation of hepatitis following chemotherapy for haematological malignancies. Seven patients had non-Hodgkin's lymphoma of whom three were treated with MACOP-B, two with BCEPP, one with PROMACE-CYTABOM and one with CHOP. Two patients had acute myeloid leukaemia and were treated with daunorubicin and cytosine arabinoside. Exacerbation of hepatitis occurred between one to four weeks following the last course of chemotherapy in eight patients. Two patients developed exacerbation of hepatitis when the dosage of prednisolone was reduced after they had ten weeks of high dose prednisolone. The outcome was fatal in six patients; all of whom developed hepatic encephalopathy. In four of these patients, alanine transaminase levels exceeded 1000 iu/l. Cytotoxic and immunosuppressive therapy permit enhanced viral replication. Withdrawal of the drugs results in partial restoration of immunocompetence and leads to rapid destruction of hepatocytes with consequent hepatic necrosis. Hence, patients who are hepatitis B virus carriers undergoing chemotherapy should be closely monitored. The fatal outcome of reactivation of chronic hepatitis B virus warrants prospective trials addressing preventive measures.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carrier State; Chronic Disease; Cyclophosphamide; Cytarabine; Daunorubicin; Disease Progression; Doxorubicin; Etoposide; Female; Hepatic Encephalopathy; Hepatitis B; Humans; Leucovorin; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prednisone; Vincristine