levoleucovorin and Sepsis

The current study evaluated the feasibility and clinical activity of a combination of paclitaxel, cisplatin, 5-fluorouracil (5-FU), and leucovorin administered on a biweekly schedule to patients with recurrent or unresectable squamous cell carcinoma of the head and neck (HNSCC).. Patients with recurrent or unresectable HNSCC were eligible if they had received a previous regimen of neoadjuvant chemotherapy, concurrent chemoradiotherapy, or no previous systemic therapy. Patients received paclitaxel (175 mg/m2 on Day 1), cisplatin (35 mg/m2 on Days 1 and 2), leucovorin (200 mg/m2 on Day 1), and 5-FU (1000 mg/m2 per day as a 48-hour continuous intravenous infusion on Days 1 and 2) every 2 weeks. Patients received subcutaneous filgrastim (300 microg per day) on Days 3-9 of each cycle. Treatment was administered on an outpatient basis for a maximum of six cycles.. Thirty-five patients received a combined total of 194 treatment cycles. Eighteen complete responses (51%) and 12 partial responses (34%) were documented, for an overall response rate of 86% (30 of 35 patients). The median progression-free survival duration was 14 months, and the median overall survival duration was 18 months. Two toxicity-related deaths were documented (one due to neutropenic sepsis and the other due to catheter-related pulmonary embolism). Grade 4 neutropenia was observed in one patient. Other severe (Grade 3 or 4) toxic effects included mucositis (14%), anemia (6%), thrombosis (6%), thrombocytopenia (3%), and neuropathy (3%).. The current dose-dense, four-agent, taxane-containing biweekly schedule was feasible and effective in patients with recurrent or unresectable HNSCC. However, given the single-center nature of the current study and the highly selected study population, further validation of these findings is recommended.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Female; Filgrastim; Fluorouracil; Granulocyte Colony-Stimulating Factor; Head and Neck Neoplasms; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neutropenia; Paclitaxel; Recombinant Proteins; Sepsis; Survival Analysis; Treatment Outcome

The prognosis in patients with primary refractory or relapsed high grade non-Hodgkin's lymphoma (NHL) is very poor--the 5-year survival being generally reported at 10%.. Multiple salvage regimens have been investigated and, while response rates of 50-80% have been noted in selected patients, the long-term prognosis remains poor. Following the encouraging results in high risk Burkitt's and Burkitt-like lymphoma using the CODOX-M and IVAC protocols, we performed a pilot study using a similar regimen in patients with primary refractory or relapsed high grade NHL.. The regimens were modified by a reduction in the intensity of intrathecal therapy. It was planned to mobilize peripheral blood stem cells following the IVAC cycle for use in subsequent autologous peripheral blood stem cell transplantation in chemosensitive patients. The initial plan was to recruit 50 patients, but the study was closed after 8 due to excessive toxicity.. We conclude that the CODOX-M/IVAC regimen is too toxic for this group of patients and does not result in better response rates than those to currently available salvage regimens.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Disease Progression; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Ifosfamide; Injections, Spinal; Lenograstim; Leucovorin; Lymphoma, Non-Hodgkin; Male; Mesna; Methotrexate; Middle Aged; Peripheral Blood Stem Cell Transplantation; Pilot Projects; Prognosis; Recombinant Proteins; Salvage Therapy; Sepsis; Treatment Outcome; Vincristine

Advanced transitional cell carcinoma (TCC) of the urothelial tract is usually fatal despite high response rates to platinum-based chemotherapy regimens. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated marked single-agent activity in TCC, and combinations of carboplatin and paclitaxel have been well tolerated in other solid tumors. Methotrexate is also active in TCC. Due to unexpectedly severe myelosuppression and mucositis when methotrexate and paclitaxel were combined, we undertook a phase I trial of paclitaxel, carboplatin, and escalating doses of methotrexate with granulocyte colony-stimulating factor and leucovorin support in advanced TCC to determine the feasibility of this combination. Nineteen previously untreated patients with locally advanced or metastatic TCC were eligible. Median age was 62 years. In sequence, paclitaxel 200 mg/m2 (3-hour infusion), carboplatin dosed to an area under the concentration-time curve of 6 mg/mL x min, and methotrexate 10 mg/m2, increasing in 10-mg/m2 increments, were administered on day 1 every 21 days. Granulocyte colony-stimulating factor 300 microg/d or 480 microg/d (in patients <60 kg or >60 kg, respectively) was administered on days 2 through 11 and leucovorin 15 mg orally every 6 hours for 3 days. At this time, the methotrexate dose has been escalated to 50 mg/m2. There were no dose-limiting toxicities in cycle 1. Sixty-eight cycles have been administered (range, one to eight cycles; median, three cycles). Significant hematologic toxicity including neutropenic sepsis (two episodes) occurred in subsequent cycles, but was infrequent. The major nonhematologic toxicity was neuropathy. Sixteen patients are evaluable for response. One patient has achieved a complete response, seven are partial responders, seven have stable disease, and one progressed on therapy. The overall response rate is 50% (95% confidence interval, 25% to 75%). The combination of paclitaxel, carboplatin, and methotrexate holds promise to be well tolerated and active in advanced TCC.

Topics: Administration, Oral; Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Carboplatin; Carcinoma, Transitional Cell; Confidence Intervals; Disease Progression; Drug Administration Schedule; Feasibility Studies; Female; Granulocyte Colony-Stimulating Factor; Humans; Infusions, Intravenous; Leucovorin; Male; Methotrexate; Middle Aged; Neoplasm Staging; Nervous System Diseases; Neutropenia; Paclitaxel; Remission Induction; Salvage Therapy; Sepsis; Urinary Bladder Neoplasms

Cervical ectopic pregnancy is an uncommon form of ectopic pregnancy. The spectrum of treatment options includes systemic medical therapy, local injection with methotrexate and/or potassium chloride, surgery, or a combination of these modalities.. A 29-year-old woman, gravida 3, aborta 2, was found to have a cervical ectopic pregnancy on ultrasound at 5+6 weeks' gestation. She presented to the hospital with vaginal bleeding. Treatment was initiated with multidose methotrexate and leucovorin rescue. She subsequently developed Gram-negative septicemia, with blood cultures growing Escherichia coli. This was managed successfully by surgical removal of the ectopic pregnancy and antimicrobial therapy.. A cervical ectopic pregnancy can be complicated by E. coli septicemia.

Topics: Abortifacient Agents, Nonsteroidal; Adult; Cervix Uteri; Escherichia coli Infections; Female; Humans; Leucovorin; Methotrexate; Pregnancy; Pregnancy, Ectopic; Sepsis

FOLFIRINOX has been shown to significantly increase both overall survival (OS) and progression-free survival (PFS) in metastatic pancreas cancer. There is limited data regarding the treatment of locally advanced pancreatic cancer. We present a retrospective study of patients with both locally advanced and metastatic pancreas cancer using FOLFIRINOX as first-line therapy in our centre.. This is a retrospective review of patients treated with FOLFIRINOX for pancreatic cancer at Princess Margaret Cancer Centre, between December 2011 and July 2014. The primary objective was to evaluate the efficacy and safety of FOLFIRINOX when used with dose modifications.. One hundred two patients were identified; 66 metastatic and 36 locally advanced. Sixty-eight per cent of patients initiated treatment with a dose reduction. The median (95% CI) OS in the metastatic group was 13.1 (6.3-16.1) months with full dose and 12.9 (10.3-30.1) months with modified dose. The median (95% CI) OS in the locally advanced group was 11.1 (6.1-not reached) months with full dose and 23 (not reached-not reached) months with modified dose. The median (95% CI) PFS in the metastatic group was 6.2 (4.9-15.2) months with full dose and 8.7 (5.7-12.9) months with modified dose. The median (95% CI) PFS in the locally advanced group was 11.1 (3.1-not reached) months with full dose and 10.4 (6.8-not reached) months with modified dose. Grade 3/4 haematologic adverse events were observed in 43% of patients. Grade 3/4 non-haematologic adverse events were observed in 28% of patients. Patient well-being significantly improved from baseline to cycle 4 (P=0.002).. Efficacy was achievable with dose-modified FOLFIRINOX in daily setting. The safety of FOLFIRINOX remains a concern with a high rate of grades 3 and 4 neutropaenia despite dose reduction.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; CA-19-9 Antigen; Camptothecin; Carcinoma, Pancreatic Ductal; Cisplatin; Combined Modality Therapy; Deoxycytidine; Disease-Free Survival; Drug Substitution; Female; Fluorouracil; Gastrointestinal Diseases; Gemcitabine; Hematologic Diseases; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Ontario; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Quality of Life; Sepsis; Treatment Outcome

Development of a second primary malignancy after an index esophageal cancer is a rare event, primarily due to short survival of patients with esophageal cancer. However, the number of long-term esophageal cancer survivors has been increasing due to advances in early detection and therapy.. We report herein a case of pancreatic adenocarcinoma that developed three years after a successfully treated early-stage adenocarcinoma of the esophagus. A 70-year-old Caucasian male presented with vague complaints of nausea, vomiting and abdominal distention, with subsequent development of jaundice. A computed tomography scan of abdomen revealed a 2.9 cm soft tissue mass in the head of the pancreas and the patient underwent a Whipple's procedure, with pathology confirming the diagnosis of pancreatic adenocarcinoma. Three years previously, the patient was successfully treated for adenocarcinoma of the esophagus via minimally invasive esophagogastrectomy. Despite chemoradiotherapy for localized disease and subsequent systemic chemotherapy for metastatic pancreatic cancer, the patient eventually succumbed to his illness.. We discuss the association between esophageal cancer and subsequent second malignancies, along with implications for surveillance and therapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Cholangitis; Combined Modality Therapy; Esophageal Neoplasms; Esophagectomy; Fatal Outcome; Fluorouracil; Gastrectomy; Humans; Irinotecan; Leucovorin; Lymphatic Metastasis; Male; Neoplasms, Second Primary; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Pancreaticoduodenectomy; Sepsis

A 25-year-old primigravida was diagnosed to be suffering from unruptured ectopic pregnancy. The serum β-human chorionic gonadotropin levels were 2851 mIU/l and the ectopic gestational sac was 2.7×2.7 cm without any fetal pole. It was decided to manage her by expectant therapy. But she received medical therapy with multidose methotrexate because of misinterpretation of expectant therapy as medical therapy. She suffered from methotrexate toxicity, which manifested as high-grade fever, vomiting, melena, oral ulcerations, pneumonitis, subconjunctival haemorrhages and skin pigmentation. She developed severe third space fluid collection and shock, which was mistaken for rupture ectopic gestation. Her haematological picture showed severe neutropaenia and thrombocytopaenia which confirmed the clinical picture to be due to methotrexate toxicity. She also developed septicaemia and candidal infection secondary to immunosuppression. She was managed in intensive care unit with ventilatory support, high-dose leucovorin and injection filgastrim. She responded well to the therapy with dramatic recovery in 4 days.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Therapeutic; Adult; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Medical Errors; Methotrexate; Neutropenia; Pregnancy; Pregnancy, Ectopic; Recombinant Proteins; Respiration, Artificial; Sepsis; Shock; Thrombocytopenia; Vitamin B Complex

The coexistence of liver cirrhosis with hepatocellular carcinoma (HCC) and colon cancer (Ca), which is a rare clinical condition, was treated in a liver transplant recipient.. A 46-year-old man, diagnosed incidentally during an ultrasound (US) examination with a 3.5-cm HCC in segment VII related to chronic hepatitis C virus (HCV), was referred for liver resection. He underwent a laparoscopic protocol evaluation for liver cirrhosis. Liver appearance and biopsy of the left lobe showed Child B/C liver cirrhosis. Because he fulfilled the Milan criteria, we suggested an orthotopic liver transplantation (OLT). During protocol colonoscopy, we discovered an ulcerative sigmoid colon Ca. Three weeks after completing the pre-OLT assessment he underwent an OLT and was discharged home on day 9 on an immunosuppressive regimen of Everolimus, Myfortic, and Prezolone. Two months after transplantation, the patient underwent a sigmoidectomy and for nearly 1 month thereafter received chemotherapy for colon Ca (6 cycles of FOLFOX:Folinic Acid+Fluorouracil+Oxaliplatin). One and a half years after OLT, patient was in good condition but presented with an increased alpha fetoprotein (a-FP) without other findings. A couple of months later we discovered a colon Ca recurrence and 3 small liver metastases. Patient underwent a bowel resection with Hartmann's procedure. Almost immediately after the last operation, he was found to suffer multiple myeloma. He underwent chemotherapy for both malignancies with good responses, but a few months later died of severe sepsis.. The relevant literature regarding treatment of liver cirrhosis complicated with HCC and synchronous colon Ca reveals poor and controversial outcomes. Our patient underwent chemotherapy immediately after colon resection in the presence of with a good functioning liver. Although his condition was satisfactory after OLT, the optimal treatment of such complicated patients is as yet uncertain.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Carcinoma, Hepatocellular; Chemotherapy, Adjuvant; Colectomy; Colonic Neoplasms; Colonoscopy; Fatal Outcome; Fluorouracil; Hepatitis C, Chronic; Humans; Incidental Findings; Leucovorin; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Male; Middle Aged; Multiple Myeloma; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Organoplatinum Compounds; Sepsis; Time Factors; Treatment Outcome

The risk of venous thromboembolism has been reported to increase when receiving bevacizumab. Many cancer patients are reported to have elevated D-dimer levels. It is not clear what D-dimer level might indicate an increased risk of venous thromboembolism in the colorectal cancer patients treated with bevacizumab-containing chemotherapy.. The D-dimer levels and any event concurrent with an elevated D-dimer level were evaluated in patients receiving bevacizumab. The D-dimer cut-off level was determined using the receiver-operating characteristic analysis. The selection criteria were as follows: histologically proven metastatic and unresectable colorectal adenocarcinoma; no prior chemotherapy containing bevacizumab; D-dimer test performed repetitively on the baseline and during bevacizumab administration; no venous thromboembolism identified at the baseline; and enhanced computed tomographic scan performed every 2 months.. Sixty-nine patients were included. The chemotherapy regimens with bevacizumab included the regimen of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), the regimen of 5-fluorouracil, leucovorin and irinotecan (FOLFIRI), and leucovorin-modulated 5-fluorouracil. The median baseline D-dimer level was 1.2 µg/ml. The appropriate D-dimer cut-off level was 3 µg/ml with the negative predictive value of 98% and relative risk of 6.9. Twenty-one of 69 patients showed elevated D-dimer levels of >3 µg/ml, with 11 patients for unknown reasons, 6 with tumor progression, 3 with venous thromboembolism and 1 with sepsis. In the remaining 48 patients whose D-dimer levels were ≤3 µg/ml, only one patient developed a venous thromboembolism.. A D-dimer cut-off level of 3 µg/ml might be a useful indicator level to exclude venous thromboembolism or show an increased risk for venous thromboembolism in colorectal cancer patients treated with bevacizumab-containing chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Disease Progression; Female; Fibrin Fibrinogen Degradation Products; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Retrospective Studies; Sensitivity and Specificity; Sepsis; Venous Thromboembolism

Prospective randomized clinical trials have shown the effectiveness of combined adjuvant 5-fluorouracil-based chemotherapy and radiotherapy after surgical resection of rectal cancer. To assess toxicity of this therapy, prospective data were collected from 236 Asian rectal cancer patients treated with combined 5-fluorouracil-based chemotherapy and radiotherapy after surgery. Almost 82% of patients completed planned therapy. Grade 3 and 4 diarrhea, stomatitis, and granulocytopenia occurred in approximately 18-21% of patients. There were two treatment-related deaths from granulocytopenia and sepsis. With median follow-up of 3.5 years, median disease-free and overall survival was 75 and 88 months, respectively. In conclusion, combined adjuvant 5-fluorouracil-based chemotherapy and radiotherapy after surgical resection of rectal cancer is tolerable in Asian patients with moderate toxicity.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Agranulocytosis; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Combined Modality Therapy; Diarrhea; Disease-Free Survival; Drug Evaluation; Female; Fluorouracil; Humans; Leucovorin; Life Tables; Lymph Node Excision; Male; Middle Aged; Neoplasm Metastasis; Postoperative Period; Prospective Studies; Radiotherapy, Adjuvant; Rectal Neoplasms; Sepsis; Singapore; Stomatitis; Survival Analysis

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Granulocyte Colony-Stimulating Factor; Humans; L-Lactate Dehydrogenase; Leucovorin; Lymphoma, Non-Hodgkin; Methotrexate; Middle Aged; Neutropenia; Sepsis; Vincristine

Short treatment with four cytostatics in acute granulocytic leukemia induced aplasia and reduction of total leukemic cells in 50 over 59 patients. Complete remission occured in 30 and 20 died with infectious complications during induction. Short induction treatment allowed a reduction of induction period and so a reduction of high risk period of induction before completion of complete remission.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cytarabine; Daunorubicin; Drug Administration Schedule; Female; Fever; Hemorrhage; Humans; Leucovorin; Leukemia, Myeloid, Acute; Male; Methotrexate; Middle Aged; Pyruvaldehyde; Remission, Spontaneous; Sepsis