levoleucovorin and Drug-Hypersensitivity

5-Fluorouracil (5-FU) is combined with folinic acid (FA) for enhancing its cytotoxic effects in the colon cancer chemotherapy treatment. Folinic acid has rarely been involved in hypersensitivity reactions. Here, we report a case of FA hypersensitivity in an adult patient initially attributed to oxaliplatin administered concurrently. A 56-year-old male patient diagnosed with colon cancer received twelve cycles of FOLFOX4, one cycle of FOLFIRI plus cetuximab and nine cycles of FOLFOX6 uneventful. At the tenth cycle of FOLFOX6 chemotherapy, after 15 minutes of starting the infusion of oxaliplatin and FA, the patient reported flushing, pruritus and abdominal pain and erythema and oedema developed over the face and thorax. After progression, FOLFIRI plus aflibercept was scheduled and another reaction occurred. At this time, FA was discontinued and the patient received another cycle consisted on irinotecan plus 5-FU without incidences. This episode of hypersensitivity reaction following FA infusion with no oxaliplatin empirically confirmed that the hypersensitivity reaction was secondary to FA. Clinicians should be aware of hypersensitivity reaction with FA, especially when FA is administered concomitantly with oxaliplatin, despite its lower risk to cause hypersensitivity reactions. Furthermore, the similar signs and symptoms associated to the hypersensitivity reactions of each agent, highlight the importance of having a specialised allergist team for to make a prompt diagnose of the causative agent in order to prevent patient harm and proceed properly without unnecessary delays in the scheduled chemotherapy treatments.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Hypersensitivity; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin

Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Hypersensitivity; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds

We report a case of a 59-year-old woman with metastatic carcinoma of the ileocecal region who received FOLFOX(oxaliplatin/leucovorin/5-fluorouracil) and bevacizumab therapy and exhibited a partial remission with minimal side effects. She developed a mild self-limited episode of immune-mediated hemolytic anemia during her 16th cycle of chemotherapy, which precluded her from receiving further oxaliplatin. We review the literature on oxaliplatin-induced immune-mediated hemolysis, including its mechanism, presenting symptoms, laboratory features, management, and implications for future therapy.

Topics: Anemia, Hemolytic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cecal Neoplasms; Drug Hypersensitivity; Female; Fluorouracil; Humans; Hypersensitivity, Delayed; Ileal Neoplasms; Intestinal Neoplasms; Leucovorin; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Treatment Outcome

The increased resistance, intolerance, or allergy to trimethoprim/sulfamethoxazole (TMP/SMX) has brought much attention to alternative treatment of pneumonia caused by Pneumocystis carinii (PCP). Pentamidine is considered when there is documented allergy or intolerance to TMP/SMX. Similarly, either dapsone/trimethoprim or clindamycin/primaquine is effective in the treatment of mild to moderate PCP, but both regimens are contraindicated in glucose 6-phosphate dehydrogenase (G6PD) deficiency. For this purpose, atovaquone should be used in patients who are deficient in G6PD or who are unable to be on TMP/SMX or pentamidine. On the other hand, in severe disease, adjunctive corticosteroids can enhance the efficacy of either TMP/SMX or pentamidine. If these therapies yield no response, trimetrexate with leucovorin has been approved as initial and salvage therapy in severe PCP. We review alternative treatment to TMP/SMX and propose ideal and practical therapeutic and prophylactic guidelines in the treatment and prevention of PCP.

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Drug Combinations; Drug Hypersensitivity; Drug Resistance, Microbial; Humans; Leucovorin; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

The effectiveness of reintroducing oxaliplatin in patients with metastatic colorectal cancer refractory to standard chemotherapy has not been verified. We performed a single-arm, open-label, Phase II study to evaluate the safety and efficacy of reintroducing oxaliplatin.. Eligible patients had received prior chemotherapy including oxaliplatin and irinotecan that achieved a response or stable disease followed by confirmed disease progression ≥6 months previously during prior oxaliplatin-based therapy. The primary endpoint was the disease control rate (DCR) after 12 weeks of treatment starting. The DCR was defined as the sum of patients with complete response, partial response, and stable disease.. Thirty-three patients were enrolled. The median age was 62 (range: 35-77) years and the male/female ratio was 19/14. Eastern Cooperative Oncology Group performance status was 0 in 84.8%. Fourteen primary tumors were in the colon and 19 were in the rectum. All patients received modified FOLFOX6 as the protocol treatment. After 12 weeks of treatment starting, the DCR was 39.4% (95% confidence interval 21.8-57.0) and the response rate (complete response and partial response) was 6.1%. The median number of chemotherapy cycles was five and the median total dose of oxaliplatin was 425 mg/m(2). Median progression-free survival time was 98 days and median overall survival was 300 days. The incidence of grade ≥1 and grade ≥3 allergic reactions was 28.1% and 3.1%, respectively. The incidence of grade ≥1 and grade ≥3 peripheral sensory neuropathy was 53.1% and 0%, respectively. There were no other severe adverse events and no treatment-related deaths.. Reintroducing oxaliplatin can be both safe and effective. This may be a salvage option for patients with metastatic colorectal cancer who achieved a response or stable disease with prior oxaliplatin-based therapy followed by disease progression ≥6 months previously during prior oxaliplatin-based therapy.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Drug Hypersensitivity; Endpoint Determination; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System Diseases; Prospective Studies; Salvage Therapy; Survival Analysis; Treatment Outcome

The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin (OXA) in combination with continuous infusional 5-fluorouracil (5-FU) and leucovorin (LV) administered every 2 weeks (modified FOLFOX-4 regimen) in elderly patients with advanced gastric cancer (AGC).. A total of 44 previously untreated AGC patients aged 65 or older were treated with OXA 85 mg m-2 on day 1, LV 200 mg m-2 as a 2-hour infusion followed by a 22-hour infusion of 5-FU 1000 mg m using a multichannel programmable pump, repeated for 2 consecutive days every 2 weeks.. All patients were assessable for toxicity and 40 patients for response. Median age was 69 years (65-83). The response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria was 52.5% (95% confidence interval: 44.6%-68.0%) with 3 complete responses, 18 partial responses, 11 stable diseases, and 8 progressions. Median time to progression was 6.5 months and median overall survival was 10.0 months. Toxicity was generally mild. Grade 3 hematologic toxicities of neutropenia, anemia, and thrombocytopenia were in 6.8%, 2.3%, and 4.5% of the patients, respectively. No grade 4 hematologic toxicities occurred. Grade 1 peripheral neuropathy was a common event (34.1%), whereas grade 3 peripheral neuropathy was recorded in only 1 (2.3%) patient. An acute hypersensitivity reaction was observed in 1 patient during administration.. The modified FOLFOX-4 regimen is an active and well-tolerated chemotherapy for elderly patients aged > or =65 years with AGC. OXA may occasionally cause mild hypersensitivity.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Hypersensitivity; Female; Fluorouracil; Follow-Up Studies; Granisetron; Hematologic Diseases; Humans; Infusions, Intravenous; Leucovorin; Male; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System Diseases; Premedication; Stomach Neoplasms; Survival Rate; Treatment Outcome

Oxaliplatin, a platinum-containing antineoplastic agent, is a key drug for the treatment of colorectal cancer and gastric cancer; however, some patients develop allergic reactions. Our hospital uses a regimen to control allergic reactions in patients with mild allergies(Grade 1 and 2). The aim of this study was to determine the effectiveness and safety of our allergy regimen. We retrospectively investigated 22 patients who initiated our allergy regimen between January 2017 and December 2017. The median number of administration cycles before allergy development was 8, and the median cumulative dose of oxaliplatin was 700mg/m2. Of the 22 patients, 18(82%)were able to continue oxaliplatin therapy. Drowsiness was the only adverse event that occurred in this cohort. Our allergy regimen may be effective for controlling allergic reactions to oxaliplatin in patients with mild allergies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Hypersensitivity; Fluorouracil; Humans; Leucovorin; Oxaliplatin; Retrospective Studies

Although hypersensitivity reactions (HSRs) to oxaliplatin (L-OHP) therapy are well-documented, few reports have compared different therapies in terms of HSR occurrence. In this study, we compared the frequency and pattern of HSRs to modified FOLFOX6 (mFOLFOX6; 5-fluorouracil, levofolinate calcium and L-OHP infusions) and XELOX (capecitabine and L-OHP) therapies, and sought to identify risk factors associated with HSRs.. Patients who had received mFOLFOX6 or XELOX chemotherapeutic regimens for unresectable colon or rectal cancer or as adjuvant chemotherapy following colon cancer surgery between April 2012 and August 2015 were included. Potential correlation between treatment modalities (regimen, dosage and route of administration of L-OHP, and injection timing for dexamethasone administration) and HSRs was assessed.. Among the 240 patients included in the study, 136 had received mFOLFOX6 therapy and 104 had received XELOX therapy. Although the frequency of HSRs did not differ between the two groups, incidence of HSRs in the first cycle was higher in the XELOX therapy group. Treatment method or cumulative dosage was not identified as a risk factor for HSR; however, the incidence of ≥grade-2 HSR was higher in cases where the cumulative L-OHP dosage was ≥600 mg/m. Although HSR rates were comparable among patients treated with mFOLFOX6 and XELOX, HSRs tended to occur more frequently during the first cycle of XELOX therapy as compared to that with mFOLFOX6 therapy. Our findings warrant careful assessment of ≥grade-2 HSRs in patients who are prescribed cumulative L-OHP dosages of ≥600 mg/m

Topics: Aged; Anti-Inflammatory Agents; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colorectal Neoplasms; Combined Modality Therapy; Deoxycytidine; Dexamethasone; Drug Hypersensitivity; Female; Fluorouracil; Humans; Incidence; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Retrospective Studies; Risk Factors

Oxaliplatin at a dose of 85 mg/m(2) traditionally has been administered over 120 min in the standard FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) regimen. CapeOx (capecitabine plus oxaliplatin), in which the dose of oxaliplatin is 130 mg/m(2), has also been infused over 120 min. Maintenance of a prolonged infusion time has been largely based on the concern for a potential hypersensitivity reaction (HSR) if administered too quickly.. We first performed a retrospective review of our institutional experience to assess whether HSR rates were similar in FOLFOX and CapeOx by using computerized pharmacy records between January 1, 2011, and December 31, 2013. We then instituted a new policy to infuse all nonresearch doses of oxaliplatin at a set rate of 1 mg/m(2)/min (85 mg/m(2) given over 85 min; 68 mg/m(2) over 68 min, etc). The incidence of HSRs with the new infusion rate was actively monitored.. Of 2,097 patients who previously received oxaliplatin over 120 min, 1,936 received a dose of 85 mg/m(2) (± 10%), and 161 received a dose of 130 mg/m(2). The incidence of HSRs in the 85 mg/m(2) group was 11% versus 7% in the 130 mg/m(2) group (P = .13). Then between December 1, 2014, and June 4, 2015, 667 patients received oxaliplatin at a rate of 1 mg/m(2)/min for all doses. The incidence of HSRs in patients treated at this fixed infusion rate was 8%.. Infusing oxaliplatin at a rate of 1 mg/m(2)/min does not increase the rate of HSRs and does not compromise patient safety. This infusion rate is safe for use in routine practice.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Drug Administration Schedule; Drug Hypersensitivity; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Hypersensitivity; Female; Fluorouracil; Humans; Leucovorin; Male; Neoplasms; Organoplatinum Compounds

Children treated for toxoplasma retinochoroiditis may experience a range of severe adverse drug responses. Drug reaction with eosinophilia and systemic symptoms syndrome is a life-threatening idiosyncratic drug reaction with a 10% mortality. We present a case of drug reaction with eosinophilia and systemic symptoms syndrome in a child on standard combination treatment with oral sulfadiazine, pyrimethamine, folinic acid, and steroids for toxoplasma retinochoroiditis. Early clinical recognition and appropriate treatment led to a complete recovery and no longterm sequelae. The parents of children during sulfadiazine treatment should be counseled on the potential significance of nonspecific illness.

Topics: Adolescent; Antiprotozoal Agents; Chorioretinitis; Drug Eruptions; Drug Hypersensitivity; Drug Therapy, Combination; Eosinophilia; Female; Humans; Leucovorin; Pyrimethamine; Steroids; Sulfadiazine; Toxoplasmosis, Ocular

Leucovorin is a reduced form of folic acid, which has multiple uses.(1) In this case report, it is used in combination with fluorouracil in the treatment of colon cancer. We describe a 53-year-old male, who was started on FOLFOX 6 + bevacizumab who experienced a hypersensitivity reaction to leucovorin. There have been very few cases of leucovorin hypersensitivity reactions reported in the literature. In this case, symptoms include flushing, hives, body pain, headaches, elevated blood pressures, and general discomfort. Although leucovorin reactions are considered rare, one should be aware of the types of reactions that can occur with leucovorin.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colonic Neoplasms; Drug Hypersensitivity; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds

Oxaliplatin hypersensitivity is a well-known adverse reaction but the prevalence varies and data for frequency and clinical features have not been reported for Korea. Here we evaluates the prevalence and risk factors for hypersensitivity reactions to oxaliplatin after chemotherapy.. Clinical information on all patients treated with oxaliplatin was retrospectively reviewed in electronic medical records between August 2009 and July 2010 in Seoul National University Bundang Hospital. Patients who experienced hypersensitivity reactions to oxaliplatin were compared with those who did not.. A total of 393 patients received oxaliplatin, with 42 (10.7%) experiencing hypersensitivity reactions including three cases of anaphylaxis. Median cycle of the first hypersensitivity reaction was 8. Reactions correlated with lower dexamethasone doses. Other variables were not significant.. The prevalence of hypersensitivity reactions was 10.7%, symptoms being mostly mild and cutaneous. Lower dexamethasone doses could be a predictor for hypersensitivity reactions to oxaliplatin.

Topics: Aged; Anaphylaxis; Anti-Inflammatory Agents; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Dexamethasone; Drug Eruptions; Drug Hypersensitivity; Female; Fluorouracil; Gemcitabine; Glucocorticoids; Histamine H1 Antagonists; Humans; Hydrocortisone; Leucovorin; Male; Middle Aged; Multivariate Analysis; Neoplasms; Organoplatinum Compounds; Oxaliplatin; Prevalence; Republic of Korea; Retrospective Studies; Risk Factors

Oxaliplatin is a third-generation platinum compound and a key agent for the management of colorectal cancer. Patients treated with oxaliplatin are at risk for hypersensitivity reactions. We designed a modified premedication regimen to prevent oxaliplatin-related hypersensitivity reactions and assessed if this approach is effective.. A retrospective cohort study of patients with advanced colorectal cancer who received modified FOLFOX6 (mFOLFOX6) was performed. Patients received routine premedication with dexamethasone 8 mg and granisetron 3 mg for the first five cycles of mFOLFOX6. From the sixth cycle onward, cohort 1 received the same premedication, and cohort 2 received modified premedication (diphenhydramine 50 mg orally, followed by dexamethasone 20 mg, granisetron 3 mg, and famotidine 20 mg). We compared the incidence of hypersensitivity reactions, duration of treatment, and reasons for treatment withdrawal between the two cohorts.. A total of 181 patients were studied (cohort 1, 81; cohort 2, 100). Hypersensitivity reactions developed in 16 patients (20%) in cohort 1 and 7 (7.0%) in cohort 2 (P = 0.0153). The median number of cycles increased from 9 in cohort 1 to 12 in cohort 2. Apart from progressive disease, neurotoxicity was the reason for discontinuing treatment in 20% of the patients in cohort 1, as compared with 53% in cohort 2.. Increased doses of dexamethasone and antihistamine significantly reduced oxaliplatin-related hypersensitivity reactions. This effective approach should be considered for all patients who receive FOLFOX, allowing treatment to be completed as planned.

Topics: Adenocarcinoma; Anti-Allergic Agents; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Colorectal Neoplasms; Desensitization, Immunologic; Dexamethasone; Drug Hypersensitivity; Fluorouracil; Histamine Antagonists; Humans; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Premedication; Retrospective Studies

Previously, we suggested that oxaliplatin (L-OHP)-related grade 3/4 hypersensitivity reactions occurred immediately after the initiation, but grade 1/2 reactions did not. This study was conducted to clarify the risk factors for L-OHP-related hypersensitivity reactions.. Clinical data from 108 Japanese patients with colorectal cancer were analyzed, who were treated with L-OHP-containing regimens, FOLFOX4 and/or mFOLFOX6. The risk factors examined included demographic data, preexisting allergies, laboratory test data, treatment regimen, treatment line of therapy, pretreatment with steroids, total number of cycles and cumulative amount of L-OHP.. The incidence of grade 1/2 and grade 3/4 hypersensitivity reactions were found at 13.0% (14/108) and 9.3% (10/108), respectively. Female (P = 0.037), preexisting allergies (P = 0.004) and lower level of lactate dehydrogenase (P = 0.003) were risk factors for grade 1/2 hypersensitivity reactions, and higher neutrophil count (P = 0.043) and lower monocyte count (P = 0.007) were for grade 3/4 reactions. Total number of cycles were larger in the patients with grade 3/4 reactions than those without reactions (P = 0.049).. Further extensive examination with a large number of patients is needed to establish a patient management strategy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Hypersensitivity; Female; Fluorouracil; Humans; Hypersensitivity; Japan; L-Lactate Dehydrogenase; Leucovorin; Leukocyte Count; Male; Middle Aged; Monocytes; Neutrophils; Organoplatinum Compounds; Oxaliplatin; Risk Factors; Sex Characteristics

Confusion still exists in the diagnosis of drug-induced immune haemolysis (DIH). The aim of this study was to demonstrate antibodies specific to 5-fluorouracil (5-FU) in a patient with fatal immune haemolysis (IH). The case of a patient who died due to protracted IH is described. A 57-year-old female underwent treatment with oxaliplatin, 5-FU and folinic acid due to cholangiocarcinoma. Following drug administration, she was transfused because of a mild non-haemolytic anaemia and died following haemolysis. Serological testing including antibody screening, direct antiglobulin test and detection of drug-dependent antibodies was performed using standard techniques. The patient's serum was observed to be red in colour due to the presence of free haemoglobin prior to and following blood transfusion, and contained antibodies reactive with RBCs only in the presence of urine from several patients treated with 5-FU (ex vivo antigens). Drug-induced immune haemolysis (DIH) and metabolite-dependent antibodies should always be taken into consideration when a patient being administered any type of drug develops haemolysis.

Topics: Anemia; Anemia, Hemolytic; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Blood Transfusion; Cholangiocarcinoma; Coombs Test; Cryoglobulins; Dialysis; Drug Hypersensitivity; Fatal Outcome; Female; Fluorouracil; Humans; Leucovorin; Low Back Pain; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Specimen Handling; Temperature

Hypersensitivity reaction (HSR) and sensory neuropathy are major complications of oxaliplatin-based chemotherapy. Preplanned withdrawal of oxaliplatin after the first six cycles and reintroduction at the time of disease progression (stop-and-go strategy) may reduce neurotoxicity. However, the effect of an oxaliplatin-free interval on HSR occurrence remains poorly understood.. Data on patients with colorectal cancer who received FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) treatment between June 2005 and June 2009 were retrieved from the prospective cohort database of the Outpatient Oncology Unit of the Kyoto University Hospital. Factor analysis was performed.. Among patients who received six or fewer cycles of FOLFOX, the incidence of HSR was low (7/99, 7.1%). For patients who received more than six cycles, the incidence of HSR was higher among patients treated with stop-and-go FOLFOX than among patients treated with continuous FOLFOX (25/61, 41.0% vs. 13/63, 20.6%; p = 0.019). Interestingly, most cases of HSR during stop-and-go FOLFOX occurred during the second or third cycle of the reintroduction phase (21/25, 84%). Multivariate analysis identified undergoing an oxaliplatin-free interval as an independent risk factor (p = 0.016).. An oxaliplatin-free interval may increase the risk of HSR. Special vigilance is needed during the second and third cycles after reintroduction of oxaliplatin.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Drug Hypersensitivity; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Logistic Models; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Risk Factors; Time Factors

Topics: Adolescent; Drug Hypersensitivity; Exanthema; Fever; Humans; Leucovorin; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Allergic reactions to oxaliplatin can be severe and are an important cause of discontinuation of treatment. A retrospective review was performed for 105 patients who received FOLFOX regimens between May 2005 and June 2007. Twenty-five cases (23.8%) of allergic reactions were identified, including 9 late onset reactions (8.6%) and 16 immediate reactions (15.2%). Severe allergy (Grades 3 and 4) occurred in seven patients (6.7%). Re-introduction of FOLFOX was attempted for seven immediate onset patients with a severity grade of 1 or 2, and three of these patients (42.9%) showed relapse of allergy. In approximately 10% of the patients, FOLFOX had to be discontinued due to allergy before the disease became refractory to the regimen. Our experience indicates that allergy to oxaliplatin may be a significant concern and that methods are required for suppression of this allergy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Hypersensitivity; Female; Fluorouracil; Humans; Japan; Leucovorin; Male; Medical Records; Middle Aged; Neoplasms; Organoplatinum Compounds; Oxaliplatin; Prognosis; Retrospective Studies; Risk Factors; Survival Rate

Topics: Aged; Anemia, Hemolytic, Autoimmune; Azathioprine; Drug Hypersensitivity; Female; Folic Acid; Humans; Leucovorin; Purpura, Thrombocytopenic, Idiopathic; Urticaria

We retrospectively investigated the frequency and severity of adverse events in 124 patients with colorectal cancer who were treated by mFOLFOX6 regimen from August, 2005 to December, 2006. The incidences of grade 3/4 adverse events were; leucopenia 16%, neutropenia 40%, anemia 11%, thrombocytopenia 7%, febrile neutropenia 7%, nausea 3%, vomiting 2%, anorexia 2%, diarrhea 4%, fatigue 7%, and alopecia 0%. The incidences of all grades and grade 3/4 hypersensitivity reaction were 35% and 4%, and the median number of course when it firstly appeared was 6(range, 1-21). The incidences of all grade and grade 3 peripheral sensory neuropathy were 74% and 6%, and the median number of course when it firstly appeared 11(range, 6-16). The incidences of adverse events in this cohort were similar or lower than those reported in Western countries. Our investigation shows that mFOLFOX6 regimen is tolerable in clinical practice in Japan. The informed consent form was revised based on these results. The incidences of adverse events were renewed to provide useful information and improve self-care ability. The symptoms and the time to appearance of the hypersensitivity reaction and peripheral sensory neuropathy were added. We think it is important to provide the information based on the clinical practice.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Hypersensitivity; Female; Fluorouracil; Humans; Informed Consent; Leucovorin; Male; Mental Competency; Middle Aged; Organoplatinum Compounds; Peripheral Nervous System Diseases; Retrospective Studies

Oxaliplatin is a platinum compound that is clinically effective for colorectal cancer (CRC), in combination with 5-fluorouracil (5-FU) and leucovorin (LV), and it is widely used for metastatic disease and for the adjuvant treatment of stage III CRC. With the increasing use of oxaliplatin in Japan, serious adverse events have been experienced other than hematologic and neurologic toxicities.. In order to clarify the clinical features of allergic reactions to oxaliplatin, we retrospectively investigated CRC patients who had received oxaliplatin-based chemotherapies.. One hundred and twenty-five CRC patients who had been treated with FOLFOX regimens (containing oxaliplatin, 5-FU, and LV) were examined, and 21 patients (17%) were found to have developed allergic reactions. Sixteen patients (13%) had grade 1/2 adverse events, classified according to the common terminology criteria for adverse events (CTC-AE) version 3.0 and 5 (4%) had grade 3/4 adverse events. The allergic reaction appeared after a median number of nine cycles (range, 2-15 cycles). Previous chemotherapy included 5-FU/LV, CPT-11, and S-1. All of the patients with allergic reactions recovered completely when treated with antiallergy drugs. Oxaliplatin was reintroduced in 11 patients, with the use of prophylactic agents; allergic reaction to the reintroduction was not observed in 8 patients and grade 1/2 allergic reactions developed in 3 patients. No correlation was identified between allergic reaction and patients' background characteristics such as sex, history of allergy, and profile of other adverse events.. Allergic reactions to oxaliplatin remain an important issue for patients being able to safely continue effective chemotherapies; further analysis will be needed to establish methods for the prediction and prophylaxis of such reactions.

Topics: Adult; Aged; Anti-Allergic Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Asian People; Colorectal Neoplasms; Drug Hypersensitivity; Female; Fluorouracil; Humans; Japan; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Retrospective Studies; Secondary Prevention; Severity of Illness Index; Treatment Outcome

We examined 155 patients who received a first-line modified FOLFOX6 ( mFOLFOX6) regimen for unresectable or recurrent colorectal cancer regarding oxaliplatin-related allergic reactions and prognosis of patients who developed such allergic reactions. Twenty eight patients (18.1%) developed a total of 44 allergic reactions (2.9%): The first allergic reactions were grade 1 in nine, grade 2 in seventeen, and grade 3 in two. The median number of cycles of mFOLFOX6 until the first allergic reaction was 8.5 (range, 1-25). Compared with non-allergic group patients (n=127), allergic group patients (n=28) had mFOLFOX6 regimen more frequently (p=0.01) and higher rate of introduction to second-line FOLFIRI regimen (p<0.01). When analysis was restricted to patients who were given a second-line FOLFIRI regimen, the response rate and disease control rate associated with FOLFIRI treatment did not differ significantly between the two groups. However, the allergic group patients tended to show longer disease-free survival (p=0.16) and showed longer overall survival after the start of second-line treatment (p=0.03). In addition, the allergic group patients showed a longer overall survival after the start of mFOLFOX6 (p=0.03). These results suggest that allergic reactions in the first-line mFOLFOX6 treatment might not be a poor prognostic factor, considering the efficacy of second-line FOLFIRI regimen.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Hypersensitivity; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Prognosis

Oxaliplatin is a therapeutic platinum compound used for the treatment of colorectal cancer; however, it might induce hypersensitivity reactions, a critical situation that requires discontinuation of chemotherapies that contain oxaliplatin. Independent attempts of oxaliplatin desensitization have been reported, with mostly successful results. This letter reports a 53-year-old Japanese woman (weight, 70 kg) with chemorefractory metastatic rectal cancer who had undergone surgical intervention twice and received 3 treatment regimens. The patient developed grade 3 hypersensitivities to oxaliplatin during cumulative cycles of the FOLFOX (5-fluorouracil/leucovorin/oxaliplatin)-4 regimen. After the subsequent regimen failed, she was desensitized using a protocol of an 8-hour series of diluted-oxaliplatin infusions. Because, according to previously published desensitization reports, hypersensitivity reactions might recur during the final bag infusion of oxaliplatin despite intensive premedication, prophylactic antiemesis, corticosteroids, and antihistamines were administered twice (ie, before and during the oxaliplatin infusion). Allergic reactions were successfully and efficiently prevented with the 2 stages of intensive premedication in this patient who was able to receive oxaliplatin and had stabilized lung metastases. She was able to undergo desensitization for 5 cycles until acute development of obstructive pneumonia. In this report of a previously sensitized patient, a type I hypersensitivity reaction was successfully circumvented with 2-staged premedication for oxaliplatin desensitization. The optimum desensitization protocol for oxaliplatin administration in terms of efficacy and tolerability still needs to be defined.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Desensitization, Immunologic; Drug Hypersensitivity; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Premedication; Rectal Neoplasms

Since the results of the MOSAIC trial demonstrated an improved disease-free survival in stage III colorectal patients treated with oxaliplatin combined with 5-fluorouracil and folinic acid when they were compared with those treated with 5-fluorouracil and folinic acid alone, the addition of this organoplatin to 5-fluorouracil and folinic acid has become first-line adjuvant treatment for stage III colorectal cancer. Unfortunately, there is a small population of patients who develop grade III/IV hypersensitivity reactions to oxaliplatin which, until recently, have interfered with further treatment with oxaliplatin-containing regimens. Successful oxaliplatin desensitization protocols for patients having severe oxaliplatin hypersensitivity reactions have been reported. However, none of these protocols, have incorporated magnesium and calcium salts. Retrospective data has suggested that pretreating colorectal cancer patients with magnesium sulfate and calcium gluconate before the administration of oxaliplatin may reduce the incidence of neurotoxicities induced by this drug. Therefore, we modified a previously published oxaliplatin-desensitization protocol by incorporating intravenous calcium gluconate and magnesium sulfate, and report a patient with stage IIIc colorectal cancer and prior severe hypersensitivity reactions to oxaliplatin who underwent successful oxaliplatin desensitization using this protocol.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Calcium Gluconate; Drug Hypersensitivity; Female; Fluorouracil; Humans; Leucovorin; Magnesium Sulfate; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Sigmoid Neoplasms; Treatment Outcome

To report 2 cases of hypersensitivity reactions associated with oxaliplatin treatment in Asian patients.. A 33-year-old Chinese woman received adjuvant oxaliplatin in combination with fluorouracil and leucovorin. Shortly during her sixth infusion, she developed a severe hypersensitivity reaction. Despite prophylactic measures, she developed another reaction of similar severity during her subsequent infusion and was not further rechallenged with oxaliplatin. The second case involved a 45-year-old Malay woman who received oxaliplatin, fluorouracil, and leucovorin for metastatic colorectal cancer. Shortly during her ninth infusion, she developed a mild hypersensitivity reaction. With prophylactic measures, she developed less marked reactions with her subsequent 3 infusions.. Hypersensitivity reactions to oxaliplatin have been reported to be between 12% and 16% in the Western population. As of April 20, 2005, there are only 2 previously published reports of hypersensitivity reactions to oxaliplatin in 6 Asian patients. The incidence rates of such reactions in different Asian ethnic groups could vary. The cumulative dose, time of exposure to oxaliplatin, and clinical features were variable and unpredictable in all of the reported Asian patients who developed hypersensitivity reactions. An objective causality assessment using the Naranjo probability scale revealed that oxaliplatin was the highly probable cause of hypersensitivity in the 2 Asian patients reported by our center.. Patients who develop mild to moderate reactions can be rechallenged with the drug administered as a slow infusion with prophylactic measures. Desensitization may allow patients who experience severe hypersensitivity reactions to oxaliplatin to further receive effective therapy for their colorectal cancer.

Topics: Adult; Anti-Allergic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; China; Chlorpheniramine; Colorectal Neoplasms; Drug Hypersensitivity; Female; Fluorouracil; Humans; Hydrocortisone; Infusions, Intravenous; Leucovorin; Malaysia; Organoplatinum Compounds; Oxaliplatin; Pregnancy; Treatment Outcome

Oxaliplatin is a platinum salt that is particularly effective in treating gastrointestinal tumours. Its increased use has resulted in emergence of allergic reactions, including anaphylactic shock. Allergic reactions to oxaliplatin documented over the last 5 years have been analysed using predefined criteria. The 42 analysed patients had cancer and received a FOLFOX regimen in first line or beyond. Two types of allergy were observed: a type I immediate allergic reaction in 39 patients in whom the most frequent signs were respiratory (50%) and cutaneous (40%); anaphylactic shock that occurred in three patients; type II allergy (immunological thrombopenia) was observed in three patients. All the toxicities were reversible on symptomatic treatment. No predictive factor was evidenced. Anaphylactic shock, is rare but serious, and must be considered in the event of any severe blood pressure decrease. For the non-life-threatening reactions, prolonging infusion duration, "Stop and Go" regimen seem to be effective means of preventing recurrence.

Topics: Adult; Aged; Aged, 80 and over; Anaphylaxis; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Hypersensitivity; Female; Fluorouracil; Humans; Hypersensitivity, Immediate; Leucovorin; Male; Middle Aged; Neoplasms; Organoplatinum Compounds; Oxaliplatin; Retrospective Studies

Oxaliplatin is a third-generation platinum analog that is used mainly to treat advanced colorectal cancer. The reported incidence of hypersensitivity reactions to oxaliplatin, especially after multiple cycles of therapy, is less than 1%. We report a patient with metastatic colon cancer who developed a hypersensitivity reaction to oxaliplatin during the sixth cycle of combination chemotherapy with oxaliplatin, high-dose 5-fluorouracil and leucovorin. The same reaction occurred again after re-exposure to oxaliplatin 2 weeks later even with prophylactic administration of steroids and H1 antihistamines. After failing third-line treatment with oral tegafur-uracil, we desensitized the patient by using a fixed-rate 24-h continuous infusion of dilute oxaliplatin (0.15 mg/ml), in addition to steroids and H1 antihistamines. He had no hypersensitivity reaction during or after that infusion or when the same concentration was infused in the same way 2 weeks later. Because his condition subsequently deteriorated and the cancer progressed, no further oxaliplatin was given. Our experience does demonstrate, however, that a fixed-rate 24-h continuous infusion of oxaliplatin in a low concentration may prevent a hypersensitivity reaction in a previously sensitized patient.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Desensitization, Immunologic; Dexamethasone; Diphenhydramine; Drug Administration Schedule; Drug Hypersensitivity; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Male; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Taiwan; Time Factors

Raltitrexed (Tomudex), a classical folate antagonist, is a selective inhibitor of thymidylate synthase (TS). It has significant single-agent activity in metastatic colorectal cancer. Severe life-threatening toxicity related to the administration of 5-fluorouracil and leucovorin is described in two patients, both of whom were not deficient in dihydropyrimidine dehydrogenase. Raltitrexed was administered to both patients with clinically acceptable side effects and allowed a TS inhibitor to be administered as part of an adjuvant program.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Aged; Antimetabolites, Antineoplastic; Colonic Diseases; Drug Hypersensitivity; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Middle Aged; Quinazolines; Thiophenes; Thymidylate Synthase

Topics: Adolescent; Adult; Antidotes; Antimetabolites, Antineoplastic; Drug Hypersensitivity; Female; Humans; Kidney; Leucovorin; Male; Methotrexate; Middle Aged