levoleucovorin and Chronic-Disease

Folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or modified FOLFIRINOX (mFFX) is the first-line standard of care for metastatic pancreatic adenocarcinoma; effective and safe treatment strategies are needed as survival remains poor. Sintilimab, a human immunoglobulin G4 monoclonal antibody for programmed cell death-1, has shown efficacy in various cancers. We evaluated the efficacy and safety of sintilimab with mFFX for metastatic/recurrent pancreatic ductal adenocarcinoma in China.. This was a single-center, randomized, controlled, open-label phase II study. Patients were assigned 1:1 to sintilimab + mFFX or mFFX (n = 55, each).. In the intention-to-treat population, median overall survivals (primary endpoint) were similar in the sintilimab + mFFX and mFFX groups: 10.9 and 10.8 months, respectively [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.69-1.68]. The objective response rate was higher [50.0% (95% CI 34.6-65.4%) versus 23.9% (95% CI 11.1-36.7%)] in the sintilimab + mFFX group (P < 0.05). Median (HR, 95% CI) progression-free survival and disease control rates (95% CI) were also similar at 5.9 and 5.7 months (0.93, 0.62-1.40), and 84.1% (72.8-95.3%) and 71.7%, (58.2-85.3%), respectively. Incidences of grade ≥ 3 treatment-emergent adverse events were 84.9% (45/53) and 74.1% (40/54), and that of grade ≥ 3 immune-related adverse events were 5.7% (3/53) and 0 in each group, respectively.. The study did not meet its primary endpoint, no clear survival benefit was observed, and the benefit of sintilimab + mFFX for advanced pancreatic cancer was not supported; however, the findings suggest that using this regimen for pancreatic cancer is feasible, has an acceptable safety profile, and leads to an objective response rate of 50%. Trial registration ClinicalTrials.Gov; NCT03977272.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chronic Disease; Fluorouracil; Humans; Leucovorin; Neoplasm Recurrence, Local; Pancreatic Neoplasms

Given that the clinical course of oxaliplatin-induced neuropathy is not well defined, the current study was performed to better understand clinical parameters associated with its presentation.. Acute and chronic neuropathy was evaluated in patients receiving adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) on study N08CB (North Central Cancer Treatment Group, Alliance). Acute neuropathy was assessed by having patients complete daily questionnaires for 6 days with each cycle of FOLFOX. Before each dose of FOLFOX and as long as 18 months after chemotherapy cessation, chronic neurotoxicity was assessed with use of the 20-item, European Organisation for Research and Treatment of Cancer quality-of-life questionnaire for patients with chemotherapy-induced peripheral neuropathy.. Three hundred eight (89%) of the 346 patients had at least one symptom of acute neuropathy with the first cycle of FOLFOX; these symptoms included sensitivity to touching cold items (71%), sensitivity to swallowing cold items (71%), throat discomfort (63%), or muscle cramps (42%). Acute symptoms peaked at day 3 and improved, although they did not always resolve completely between treatments. These symptoms were about twice as severe in cycles 2 through 12 as they were in cycle 1. For chronic neurotoxicity, tingling was the most severe symptom, followed by numbness and then pain. During chemotherapy, symptoms in the hands were more prominent than they were in the feet; by 18 months, symptoms were more severe in the feet than they were in the hands. Patients with more severe acute neuropathy during the first cycle of therapy experienced more chronic sensory neurotoxicity (P < .0001).. Acute oxaliplatin-induced neuropathy symptoms do not always completely resolve between treatment cycles and are only half as severe on the first cycle as compared with subsequent cycles. There is a correlation between the severities of acute and chronic neuropathies.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Calcium Compounds; Chronic Disease; Colonic Neoplasms; Double-Blind Method; Fluorouracil; Humans; Leucovorin; Magnesium Compounds; Neurotoxicity Syndromes; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System Diseases

Oxaliplatin is a key part of the standard treatment for colorectal cancer which is formally contraindicated in patients with severe renal dysfunction. Here, we investigated a safe and efficient dosing schedule of oxaliplatin in folinic acid, fluorouracil, and oxaliplatin (FOLFOX) regimen by monitoring total and free platinum concentrations in plasma.. A 47-year-old female with chronic hemodialysis was diagnosed with left-sided colon cancer and underwent colectomy. One year later, she was presented with omentum metastasis and needed further treatment.. The computed tomography (CT) scanning revealed multiple omental nodules. Positron emission tomography-CT (PET-CT) showed increased uptake of the nodules.. The patient was treated with FOLFOX therapy every 3 weeks. The oxaliplatin began with 50 mg/m and gradually increased 85 mg/m as in the standard regimen. A 4-hour dialysis was started 1 hour after the end of oxaliplatin infusion.. The free platinum concentration time curve showed a biomodel pattern. The Cmax of the 1st peak we observed in our patients at the standard dose is comparable to patients with normal renal function. This patient was treated with FOLFOX for 12 courses. No apparent adverse effect was observed during the treatment.. The FOLFOX can be safely administered in hemodialysis patients on a long-term basis. Dose reduction of oxaliplatin is not necessarily needed if hemodialysis is performed soon after the infusion. Further studies are needed to distinguish between active and inactive oxaliplatin products during the 2nd peak of the free platinum concentration curve in this population.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chronic Disease; Colonic Neoplasms; Dose-Response Relationship, Drug; Female; Fluorouracil; Glomerulonephritis; Humans; Leucovorin; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Renal Dialysis

Chronic peripheral neuropathy is a major adverse response to oxaliplatin-containing chemotherapy regimens, but there are no established risk factors pertaining to it. We investigated the efficacy of hyperacute peripheral neuropathy (HAPN) as a predictor of oxaliplatin-induced persistent peripheral neuropathy (PPN).. Forty-seven cases of stage III colorectal cancer who received adjuvant chemotherapy with oxaliplatin after curative surgery between January 2010 and August 2014 were retrospectively reviewed. HAPN was defined as acute peripheral neuropathy (APN) occurring on day 1 (≤24 h after oxaliplatin infusion) of the first cycle. PPN was defined as neuropathy lasting >1 year after oxaliplatin discontinuation.. HAPN was found to be a predictor of oxaliplatin-induced PPN.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Chronic Disease; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Multivariate Analysis; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System Diseases; Predictive Value of Tests; Retrospective Studies; Risk Factors

Nasal Type T/natural killer (NK)-cell lymphomas are rare clinical entities, highly aggressive with a very poor prognosis. We present a case of a 37-year-old immunocompetent man presenting with deep palatal ulceration and a 3-month history of symptoms, which appear to have been misdiagnosed by physicians. The final diagnosis was achieved by a 15-day diagnostic algorithm, during which time the clinical status of the patient worsened severely. In this article, we also provide a succinct update on the clinical and histopathological findings of Peripheral T/NK-cell lymphomas and propose that symptoms that are consistent with these clinical entities should be considered from the early stages to inform a suitable diagnostic pathway Because of their highly aggressive behavior, we suggest that early therapy of T/NK-cell lymphomas may be started before completing the specific diagnostic investigations.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Chronic Disease; Delayed Diagnosis; Dexamethasone; Diagnostic Errors; Etoposide; Fistula; Humans; Ifosfamide; Leucovorin; Lymphoma, Extranodal NK-T-Cell; Male; Maxillary Sinusitis; Methotrexate; Mouth Diseases; Nose Diseases; Nose Neoplasms; Palatal Neoplasms; Radiotherapy

We sought to predict oxaliplatin-associated peripheral neuropathy during modified FOLFOX6 (mFOLFOX6) therapy.. Equal numbers of male and female patients with previously untreated, primary or recurrent colorectal cancer were followed through a first course of mFOLFOX6 with 85 mg/m² oxaliplatin every 2 weeks. Accounting for correlation among a subject's cycle, logistic regression estimated per cycle risk of acute (under 14 d) and persistent (14 d or more) neuropathy. Proportional hazards regression predicted time to persistent neuropathy.. Among mFOLFOX6 recipients (n = 50, age 58.9 ± 10.1 y), 36% received concomitant bevacizumab. Of the total number of cycles, 94.2% (422/448) were evaluable. Most (84%) subjects reported neuropathy at least once; 74% reported acute and 48% reported persistent symptoms. On multivariate analysis, risk factors shared by acute and persistent neuropathy were body surface area >2.0, acute neuropathy in a past cycle, and lower body weight. In addition, risk of acute neuropathy decreased with age (adjusted for renal function and winter season), whereas risk of persistent neuropathy increased with cumulative dose of oxaliplatin and persistent neuropathy in a past cycle. Concomitant bevacizumab was not a risk factor when administered in stage IV disease but was associated with persistent neuropathy when administered experimentally in stage III. Females had no increased risk of either form of neuropathy. After 3 cycles, weight, body surface area, and prior acute neuropathy predicted time to persistent neuropathy.. Routinely available clinical factors predict acute and persistent neuropathy associated with oxaliplatin. When validated, the proposed prognostic score for persistent neuropathy can help clinicians counsel patients about chemotherapy.

Topics: Acute Disease; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chronic Disease; Cohort Studies; Colorectal Neoplasms; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Multivariate Analysis; Organoplatinum Compounds; Peripheral Nervous System Diseases; Predictive Value of Tests; Pyridines; Retrospective Studies; Risk Assessment; Time Factors; Treatment Outcome

Long-term hemodialysis is considered to be a significant risk factor for cancer, but little is known about the use of oxaliplatin in patients on chronic hemodialysis. A 58-year-old man on chronic hemodialysis was treated for unresectable rectal cancer with synchronous hepatic metastasis by FOLFOX6 therapy with therapeutic drug monitoring. Plasma levels of total platinum, ultrafiltrate (free) platinum and 5-fluorouracil were monitored from the start of oxaliplatin administration to 120 h after the end of oxaliplatin infusion. Pharmacokinetic data of free platinum showed a bimodal pattern, decreased rapidly during the first dialysis and subsequently rose until 48 h after oxaliplatin infusion. The free platinum area under the curve was 15.7-18.9 microg h/ml when 40 mg/m(2) of oxaliplatin was administered, which was comparable to the area under the curve at 85 mg/m(2) in patient with normal renal function. The total platinum level reached a peak immediately before dialysis and gradually decreased. The 5-fluorouracil level decreased rapidly after the start of dialysis and remained constant during the continuous infusion of 5-fluorouracil. Tumor response was judged to be stable disease for >6 months, and no peripheral neuropathy or other toxicity was observed even after 11 courses. FOLFOX6 therapy with reduced dose of oxaliplatin had been safely performed for >6 months without any severe toxicity. The serum levels of free platinum showed bimodal pattern, and this second peak increased the area under the curve of free platinum. This pattern seems to be unique in patients on hemodialysis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Chronic Disease; Drug Monitoring; Fluorouracil; Glomerulonephritis; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Renal Dialysis

We present a male patient with a perianal fistula of 30 years' duration that had been treated on several occasions. The patient presented with mucoid anal adenocarcinoma. He was treated with preoperative neoadjuvant chemotherapy (5-FU and leucovorin) and external radiation therapy plus laparoscopy-assisted abdominoperineal amputation. Mucoid adenocarcinoma on chronic perianal fistula is an infrequent process. Late diagnosis is associated with a poor prognosis.

Topics: Adenocarcinoma, Mucinous; Antimetabolites, Antineoplastic; Anus Neoplasms; Chemotherapy, Adjuvant; Chronic Disease; Combined Modality Therapy; Digestive System Surgical Procedures; Fluorouracil; Humans; Laparoscopy; Leucovorin; Male; Middle Aged; Perineum; Radiotherapy, Adjuvant; Rectal Fistula

Topics: Adult; Anemia, Hypochromic; Arthroplasty, Replacement, Hip; Chronic Disease; Colitis; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Ferric Compounds; Folic Acid; Humans; Intestinal Polyps; Leucovorin; Malabsorption Syndromes; Male; Methotrexate; Osteoarthritis, Hip; Preoperative Care; Recombinant Proteins; Rectal Diseases; Remission Induction; Spondylitis, Ankylosing; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

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

A study was performed to determine whether the addition of folinic acid to a combination of methotrexate (MTX) and cyclosporin A (CsA) after allogeneic bone marrow transplantation (BMT) could improve tolerance to the regimen without inhibiting its ability to prevent graft-versus-host disease (GVHD). Sixty-nine adult BMT patients received CsA plus MTX 15 mg/m2 on day 1 and 10 mg/m2 on days +3, +6 and +11. Folinic acid 5 mg was started 24 h after each MTX dose and continued 6 hourly until 12 h before the next dose of MTX. The median age of the group was 37 years and 13 patients (19%) received bone marrow from mismatched and/or unrelated donors. No MTX doses were omitted or modified. Grade II-IV acute GVHD occurred in 18 patients (29%) and chronic GVHD in 35 of 56 (64%) patients at risk. There were no cases of grade > or = III stomatitis. Transplant-related mortality was 7% before 100 days and 20% overall (9% for low risk leukaemia) with a median follow-up of 41 months (range 24-88 months). This regimen of folinic acid rescue may contribute to a well tolerated GVHD prophylaxis protocol with reasonably low BMT-related mortality. Our results suggest that the ability of MTX to prevent acute GVHD is not abrogated by folinic acid given in this way.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Bone Marrow Transplantation; Chronic Disease; Cyclosporine; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Graft vs Host Disease; Humans; Leucovorin; Leukemia; Male; Methotrexate; Middle Aged; Transplantation, Homologous

The clinical aspect of congenital toxoplasmosis is sometimes typical, sometimes atypical. The advantage of the serological study of the aqueous is an early diagnosis and an early treatment for less expense. The classical treatment relies on the therapeutic association Pyrimethamine + Adiazine + corticosteroids which will be used during acute phases, at ordinary doses, but may be prolonged further over many months in difficult cases. Severe forms are those that are spontaneously severe or increased with the exclusive use of corticosteroids in previous attacks, noticeably when injected by local route, and in bilateral forms. Prevention of ocular toxoplasmosis is represented by the detection of sero-conversion in mother and treatment in the newborn. Due to the legal aspect of this procedure in France, the incidence of congenital toxoplasmosis has already decreased during the past years and will continue to diminish in the next future. However the possibility of acquired forms cannot be excluded, even in non immuno-depressed patients.

Topics: Adrenal Cortex Hormones; Chronic Disease; Drug Therapy, Combination; Humans; Infant, Newborn; Leucovorin; Pyrimethamine; Toxoplasmosis, Ocular

Active, recurrent, protracted toxoplasmic retinochoroiditis that had been unresponsive to intensive medical therapy with pyrimethamine, sulfamethoxypyridazine, intramuscular folicic acid, or clindamycin and corticosteroids, was treated with photocoagulation in five eyes. Four eyes healed rapidly within a few weeks. In one patient's eye, lens and vitreous opacities prevented adequate treatment with the red III intensity level of the xenon are photocoagulator. Subsequent surgical diathermy and cryocoagulation resulted in prompt healing of the lesion. Noninvasive photocoagulation of active toxoplasmosis retinochoroiditis is recommended in protracted cases if the media are clear, the macula is threatened, or there are severe complications from systemic medications.

Topics: Adolescent; Adult; Chorioretinitis; Chronic Disease; Drug Therapy, Combination; Female; Humans; Leucovorin; Light Coagulation; Male; Middle Aged; Prednisone; Pyrimethamine; Sulfadiazine; Toxoplasmosis, Ocular

The majority of clinically recognizable acute infections in the neonate are bacterial. Such infections may be acquired from the mother prior to or at birth or from environmental sources. Because of the limited ability of neonates--especially those born prematurely--to express symptoms, even minor deviations from normal behavior should suggest bacterial disease. Chronic congenital and perinatal infections, unlike acute bacterial disease, are generally asymptomatic in mother and neonate and may remain latent or subclinically active in host tissue for prolonged periods, possibly causing insidious injury to the central nervous and perceptual systems. When overt, these infections almost invariably cause mental or perceptual handicaps or both. In view of the significant mortality and morbidity associated with either acute or chronic infections, diagnosis and treatment should be aggressive.

Topics: Acute Disease; Anti-Bacterial Agents; Bacterial Infections; Chronic Disease; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Infections; Leucovorin; Penicillin G Benzathine; Pyrimethamine; Sulfadiazine; Syphilis; Toxoplasmosis