Mechanisms for acquired activated protein C resistance in cancer patients.
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Activated Protein C Resistance↗
Biomedical subjects
N Haim
Publications and source records attributed to N Haim.
Adverse interaction between capecitabine and warfarin resulting in altered coagulation parameters and bleeding: case report and review of the literature.
Capecitabine can interact with warfarin, resulting in altered coagulation parameters and bleeding. Four cases have been reported. We describe a fifth case with life-threatening interaction between these two drugs. A 67-year-old female with metastatic breast cancer developed hemorrhagic blisters, purpura and ecchymoses. She had been well controlled on long-term warfarin (5 mg/day). Capecitabine was initiated 4.5 weeks prior to the bleeding episode. Laboratory work-up revealed an international normalized ratio of 8.56, partial prothrombin time of 61 seconds and prothrombin time of 5.2%. The coagulation parameters gradually normalized within 4 days following vitamin K administration and discontinuation of capecitabine and warfarin. Careful monitoring of coagulation parameters and proper adjustment of the warfarin dose are required in patients taking warfarin and capecitabine concomitantly.
Aged↗
[Cancer in Israel: mass mediated reality vs. real reality].
BACKGROUND: Cancer, being a terminal and often incurable disease, is a source of fear and concern for human beings. One of the most important sources of medical information in general, and cancer specifically, is the mass media. The media can shape beliefs regarding health and influence people's decision-making. The main hypothesis guiding this study, based on the theoretical framework of cultivation research, is that there will be considerable differences between media coverage and medical data regarding cancer in the Israeli population. METHOD: A systematic content analysis was applied to test this hypothesis, examining all the press reports (650 articles) published during the year 2000 in three of Israel's most popular daily newspapers--"Yedioth Ahronot", "Maariv" and "Haaretz". Data from the Israeli Ministry of Health was used for comparison with media reports to the population in terms of the types of cancer reported, the emphasis on death in the context of the disease, reports concerning treatment, and the age of cancer patients. RESULTS: The findings of the study are in accordance with the main hypothesis and show that the media's portrayal of cancer does not always reflect the medical reality regarding the above mentioned aspects. Several possible explanations are proposed in analyzing these findings, focusing mainly on the nature of news making and media selection, as well as on the impact of various interest groups such as pharmaceutical companies, hospitals. laboratories, oncology departments, and various organizations trying to promote awareness and raise funds for research. CONCLUSION: The findings of this study enhance a wide range of research in different areas of human knowledge that have documented processes of constructing "mass-mediated realities", but in the case of a fatal disease, the findings may have acute implications.
Humans↗
Primary lymphoma of bone--a retrospective study. Experience at the Northern Israel Oncology Center (1979-2000).
OBJECTIVE: This retrospective study describes our experience with the diagnosis, treatment, results and long-term follow-up of primary bone lymphoma (PBL). PATIENTS AND METHODS: Nineteen patients diagnosed with PBL were reviewed. Seven patients presented with stage I(E) disease, four with stage II(E) (regional lymphadenopathy), and eight with stage IV disease (disseminated bone involvement). Only one stage IV patient exhibited 'B' symptoms. The majority (72%) demonstrated diffuse, large cell, B-type lymphoma. All patients were treated with adriamycin-based chemotherapy and consolidation radiotherapy to the primary site (8 patients: early PBL) or the most bulky area (3 patients: stage IV PBL). RESULTS: Ten stage I(E)/II(E) patients are alive with no evidence of disease (NED) and only one died due to metastatic secondary lung cancer while with NED from his PBL. Eight stage IV patients are alive with NED. Median follow-up for all living patients: 77 months. Side effects were mild and did not necessitate delay in treatment. CONCLUSIONS: Our departmental policy of treating PBL patients with an anthracycline-based regimen and involved field radiotherapy proved to be successful in achieving excellent long-term, disease-free survival. Phase III randomized, controlled, clinical trials will determine the true role of consolidation radiotherapy in PBL, when considering severe late side effects, including radiation-induced bone tumors.
Adolescent↗
Etoposide, doxorubicin and cisplatin alternating with 5-fluorouracil, doxorubicin and high-dose methotrexate in patients with advanced adenocarcinoma of the stomach or the gastroesophageal junction.
Both the etoposide, doxorubicin, cisplatin (EAP) and 5-fluorouracil, doxorubicin, high-dose methotrexate (FAMTX) schedules have been reported to be active in advanced gastric cancer. Since these regimens include non-cross resistant agents, a regimen that consists of EAP alternating with FAMTX may have an advantage over each regimen alone. We undertook a phase II trial to evaluate EAP/FAMTX in patients with advanced adenocarcinoma of the stomach or gastroesophageal junction. Of the 56 patients treated, an objective response was observed in 34%, including complete response in 7%. Median response duration was 8 months and median survival for the entire group was 9 months. The main toxicity was myelosuppression. Hospitalization for granulocytopenic fever was required in 32% of patients and 34% required red blood cells (RBC) transfusion. Non-hematological toxicity was moderate. There were three drug-related deaths associated with granulocytopenic fever. We conclude that the alternating EAP/FAMTX regimen is associated with occasional lethal events and has no obvious advantage over either regimen alone.
Adenocarcinoma↗
Acquired activated protein C resistance is common in cancer patients and is associated with venous thromboembolism.
PURPOSE: Cancer patients have an increased risk for venous thromboembolism. Because activated protein C resistance is a common risk factor for venous thromboembolism, we prospectively evaluated the activated protein C sensitivity ratio and factor V Leiden mutation in cancer patients with and without venous thromboembolism. SUBJECTS AND METHODS: We studied 55 consecutive cancer patients with deep vein thrombosis, 58 cancer patients with no history of venous thromboembolism, 54 patients with venous thromboembolism without malignancy, and 56 healthy controls. The presence of factor V Leiden mutation was determined by polymerase chain reaction and allele specific restriction digestion. The activated protein C sensitivity ratio was expressed as the ratio of activated partial thromboplastin times measured in the presence and absence of activated protein C; a ratio <2.0 in patients who did not have factor V Leiden was considered to indicate acquired activated protein C resistance. RESULTS: The prevalence of factor V Leiden mutation in cancer patients with thromboembolism (1 of 55, 2%) did not differ significantly from those in cancer patients without thromboembolism (4 of 58, 7%) or normal controls (2 of 56, 4%), but was significantly lower than that of patients with thromboembolism without cancer (18 of 54, 33%, P <0.001). The prevalence of acquired activated protein C resistance was significantly greater in cancer patients with thromboembolism (29 of 54, 54%, P = 0.001) compared with the other groups: 9 of 54 (17%) in cancer patients without thromboembolism, 7 of 36 (19%) in patients with thromboembolism without cancer, and none of the normal controls. CONCLUSION: Although factor V Leiden is not a major risk factor for thrombosis in cancer patients, acquired activated protein C resistance is common and may contribute to the thrombotic tendency in these patients.
Activated Protein C Resistance↗
Octreotide in the treatment of severe chemotherapy-induced diarrhea.
BACKGROUND: Chemotherapy-induced diarrhea (CID) is a common side effect of a number of chemotherapeutic agents. Conventional therapy for severe CID with opioids or loperamide is moderately effective. A prospective trial was conducted using octreotide acetate for treatment of severe CID refractory to loperamide. PATIENTS AND METHODS: Thirty-two patients with grade 2 and 3 CID refractory to loperamide were treated with octreotide at a dosage of 100 microg subcutaneously 3x/day for three days followed by 50 microg 3x/day for three days. Previous chemotherapy consisted of regimens containing fluorouracil, leucovorin, CPT-11, cyclophosphamide, methotrexate and cisplatin. Primary tumors were colorectal (n = 23), gastric (n = 3), and other cancers (n = 6). RESULTS: Complete resolution of diarrhea was obtained in 30 of 32 patients (94%); 5 within 24 hours, 14 within 48 hours, and 11 within 72 hours of treatment. Nineteen patients were treated as outpatients. Thirteen were hospitalized for a median of three days. Response was unaffected by age, gender, performance status, previous chemotherapy or primary tumor site. No side effects related to octreotide were observed. CONCLUSIONS: Octreotide 100 microg subcutaneously 3x/day for three days is an effective, safe treatment for CID given primarily or as a second-line therapy after loperamide failure.
Adult↗
Cancer and thrombosis revisited.
Remarkable progress has been made since the first description of the association between cancer and thrombosis by Trousseau over 100 years ago. Now, it is clear that there is a two-way connection between coagulation and cancer as tumor results in alterations in hemostatic balance, and thrombosis may promote tumor cell growth. A variety of clinical thrombotic syndromes may present in cancer patients including local and systemic venous and arterial thromboses. More evidence is now being gathered on the potential of antithrombotic regimens to prolong survival of cancer patients. Whether the use of novel antithrombotic drugs may result in a better outcome remains to be determined.
Fibrinolytic Agents↗
[The chemotherapeutic treatment of advanced Hodgkin's disease].
Between 1972 and 1994, 121 adult patients with advanced Hodgkin's disease received MOPP (M) combination chemotherapy, MOPP alternating with ABVD (M-A) or MOPP and ABV hybrid (M/A). Radiation therapy was given to 1/3 of them. The median age was 35 years, 58% had stage III and 42% had stage IV disease. Failure-free survival at 10 years was 43.9%. It was 66.7%, 48.4% and 29.9% for patients treated by M/A, M-A and M, respectively. Overall survival at 10 years was 40.8%, and 78.2%, 48% and 27.7% for patients treated by M/A, M-A and M, respectively. Multivariate analysis found age (above or below 65 years) and combination chemotherapy (with or without adriamycin) to be significant prognostic factors. M/A combination was more myelotoxic, while M combination caused more second primaries. Today, 80% of patients with advanced Hodgkin's disease may be cured, with low rate of long-term toxicity.
Adolescent↗
The incidence of lymphoma in first-degree relatives of patients with Hodgkin disease and non-Hodgkin lymphoma: results and limitations of a registry-linked study.
BACKGROUND: The precise incidence of familial Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) in first-degree relatives is unknown. Through record linkage using two population-based sources, the authors estimated the risk of HD and NHL in family members of lymphoma probands. METHODS: The authors identified 8,037 first-degree relatives of 2,606 lymphoma cases (28.5% HD, 71.5% NHL) treated between 1970 and 1993 in 3 hospitals in Israel via the family file of the Population Registry. The authors linked this file with the Israel Cancer Registry, then calculated the standardized incidence ratio (SIR) by dividing the observed number of cases with the expected, adjusting for age, gender, calendar year, and continent of origin. RESULTS: The family file yielded incomplete ascertainment of relatives (for 771 probands, no relatives were identified). Twenty cases of lymphoma--6 HD and 14 NHL--were identified among relatives of lymphoma patients. The SIR for HD was 1.15 (95% confidence interval [CI]: 0.42-2.51) and for NHL 1.71 (95% CI: 0.93-2.87), considering the entire population of first-degree relatives. SIRs among siblings of lymphoma probands were 3.12 (95% CI: 1.01-7.29) for HD, 2.16 (95% CI: 0.45-6.31) for NHL, and 2.68 (95% CI: 1.15-5.27) for all lymphomas. There were 4 HD/HD, 1 NHL/NHL, and 3 NHL/HD sibling pairs. For HD/HD and NHL/NHL sibling pairs, the interval between lymphoma occurrence in proband and sibling was 1-4 years, whereas for HD/NHL pairs this ranged from 16 to 21 years. CONCLUSIONS: The risk of lymphoma among siblings of lymphoma probands was over 2.5-fold that of the general population and lower among other family members. The temporal proximity of HD/HD and NHL/NHL sibling pairs argues for environmental as well as genetic etiology. This method was hampered by incomplete data.
Adolescent↗
Clinical activity of cisplatin and prolonged oral administration of etoposide in previously treated, anthracycline-resistant, metastatic breast cancer patients: a phase II study.
BACKGROUND: This phase II study evaluates the antitumor activity and tolerance of cisplatin and prolonged oral administration of etoposide in metastatic breast cancer previously exposed to anthracyclines. PROCEDURE: Twenty-seven patients with metastatic breast cancer who developed tumor progression following anthracyclines wer e entered in the study. The patients were treated with combination chemotherapy of cisplatin 50 mg/m(2) IV day 1 and oral etoposide 50 mg/m(2) days 1-17. Cycles were repeated every 29 days. RESULTS: Twenty-six patients were evaluated for toxicity and response. Complete remission was observed in 1 of 26 (4%) patients and partial remission in 12 of 26 (46%). Median duration of response was seven months. Pain relief was noted in 9 of 15 (60%) of the symptomatic patients. Myelosuppression was the major toxicity encountered and four (15%) patients required hospitalization for granulocytopenic fever. Nonhematologic toxicity was mild. CONCLUSIONS: The combination of cisplatin with prolonged oral etoposide is active and tolerable in the management of patients with relapsed metastatic breast cancer previously treated with an anthracycline-based regimen.
Administration, Oral↗
Echocardiography in nonbacterial thrombotic endocarditis: from autopsy to clinical entity.
Bacteria-free verrucae, frequently termed "non-bacterial thrombotic endocarditis," have been recognized in autoimmune disorders as well as in neo-plastic diseases. The antemortem diagnosis of non-bacterial thrombotic endocarditis is rare, and most existing data result from postmortem examinations. In 3 prospective echocardiographic studies we found typical cardiac valvular lesions in patients with primary antiphospholipid syndrome, myelo-proliferative disorders, and solid malignant tumors. Cardiac lesions associated with these 3 different entities had common echocardiographic appearance and correlated positively with thromboembolic events. The possibility of common pathogenesis is suggested, and clinical significance is discussed.
Antiphospholipid Syndrome↗
Aggressive non-Hodgkin lymphoma: early prediction of outcome with 67Ga scintigraphy.
PURPOSE: To evaluate use of gallium 67 scintigraphy early during chemotherapy to predict the outcome in patients with aggressive non-Hodgkin lymphoma. MATERIALS AND METHODS: Among 118 patients, 67Ga scintigraphy was performed after one cycle of chemotherapy in 51 patients, after a median of 3.5 cycles in 97 patients, and both in 30 patients. Computed tomography (CT) was performed after a median of 3.5 cycles of treatment in 87 patients. The failure-free survival was compared between patients with positive or negative 67Ga or CT scans by using the log-rank test. Multivariate analysis helped determine the relation between 67Ga scintigraphic and CT findings and the outcome. RESULTS: The differences in failure-free survival between patients with positive versus negative 67Ga scans after one cycle of treatment (P < .001) and at midtreatment (P < .001) were significant. There was no statistically significant difference in failure-free survival between patients with positive versus negative CT findings during treatment. In multivariate analysis, 67Ga scintigraphy after one cycle (P < .045) and at midtreatment (P < .006) was an independent factor associated with outcome. CONCLUSION: Gallium 67 scintigraphic findings after one cycle of chemotherapy and at midtreatment are predictive of outcome in patients with aggressive non-Hodgkin lymphoma. CT findings are not predictive. Early 67Ga scintigraphy during chemotherapy is a good indicator of patients who may benefit from a change to a more aggressive treatment. A future study is necessary to investigate the potential effect of early change of treatment.
Adolescent↗
[Preservation of the larynx in advanced cancer--experiences at the Oncology Department, Rambam Medical Center, Haifa].
The effectiveness of sequential chemo-radiotherapy in preserving the larynx in advanced laryngeal carcinoma was assessed. 4 unselected patients (19 men and 2 women, mean age 60 years) with advanced squamous cell carcinoma of the larynx (T3-4/N0-3) received induction chemotherapy consisting of 2-3 cycles of cisplatin (100 mg/m2) and 5-fluorouracil (1000 mg/m2/day) as a continuous infusion on days 1-5, followed by definitive radiotherapy: 50 Gy to the whole neck, 70 Gy to the larynx and clinically involved nodes, using a combination of 6 MV photons and 9-12 MeV electrons. 19 of the 21 patients responded to combined therapy but there was no response to induction therapy in 2 (10%) and 2 did not complete therapy due to severe toxicity. At a mean follow-up of 40 months, 7 had undergone total laryngectomy (33%), for an overall 5-year laryngeal preservation rate of 66%. Reasons for total laryngectomy in 2 patients were no response, and in 5 tumor recurrence. Mean survival was 39 months (range 11-46 months); at last follow-up, 17 of 21 were alive and disease-free, 11 of whom had a functional larynx (65% of survivors). 2 had died due to disease progression and due to a cardiovascular event. Sequential chemo-radiation allows laryngeal preservation in about 2/3 of surviving patients without compromising survival.
Antineoplastic Combined Chemotherapy Protocols↗
Dexamethasone, cytarabine, ifosfamide, and cisplatin as salvage therapy in non-Hodgkin lymphoma.
The authors conducted a phase II study to evaluate a new combination of chemotherapeutic drugs that includes dexamethasone, cytarabine, ifosfamide, and cisplatin as salvage therapy in non-Hodgkin lymphoma after prior exposure to both adriamycin and etoposide. All drugs were administered intravenously over 4 consecutive days. The daily dose of dexamethasone was 20 mg twice daily. The maximal daily doses of cytarabine, ifosfamide, and cisplatin were 75 mg/m2, 1,200 mg/m2, and 20 mg/m2, respectively. Cycles were repeated every 3 weeks. A total of 31 patients were entered in the trial. Thirty patients were evaluable for response. A complete response was seen in 11 patients (37%), and a partial response was noted in six patients (20%). A significantly higher complete response rate was seen in patients with relapsing non-Hodgkin lymphoma compared with those who failed to achieve a complete response with the last chemotherapy (10/14 vs. 1/16; p < 0.013). A complete response continues in two patients who received consolidation with high-dose chemotherapy for more than 49 months and more than 60 months for each patient. Median time to treatment failure and median survival were 3.3 months and 7.5 months, respectively, for the entire group and 11 months and 30 months, respectively, for complete responders. Myelosuppression was pronounced but was usually of short duration. Neutropenic fever developed in 13 patients (42%) and in 15 of 96 cycles (16%). Platelet transfusions were required in seven patients (23%). There was one drug-related death associated with myelotoxicity. Nonhematologic toxicity was not dose limiting. The authors conclude that dexamethasone, cytarabine, ifosfamide, and cisplatin is active and a relatively tolerable regime for patients with non-Hodgkin lymphoma previously treated with adriamycin and etoposide.
Adult↗
Sustained complete remission after chemobiohormonal therapy for metastatic melanoma.
The combination of carmustine, cisplatin, dacarbazine, interferon, and low-dose tamoxifen is widely used in treating metastatic melanoma and was originally reported to achieve a 20% complete response rate. Among 29 patients who completed the authors' phase II study with the regimen, five (17%) achieved complete remission, and the median duration of response was 8 months (range, 2-14 months). The aim of the study was to evaluate briefly the value and toxicity of this regimen in treating metastatic malignant melanoma.
Antineoplastic Combined Chemotherapy Protocols↗
Hodgkin disease: prediction of outcome with 67Ga scintigraphy after one cycle of chemotherapy.
PURPOSE: To investigate gallium 67 scintigraphy performed early during treatment as a means to predict outcome and thus to optimize treatment of Hodgkin disease (HD) in the future. MATERIALS AND METHODS: Ninety-eight patients with HD were examined. Thirty-one patients underwent 67Ga scintigraphy after one chemotherapy cycle and 83 patients after a mean 3.5 cycles (range, 2-5 cycles). Sixteen patients underwent 67Ga scintigraphy both after one cycle and at midtreatment. Patients underwent whole-body scintigraphy and single photon emission computed tomography of the torso. Torso computed tomography (CT) was performed after a mean 3.5 cycles (range, 2-6 cycles). Failure-free survival was compared between patients with positive and patients with negative test findings (Kaplan-Meier method), and the significance of the difference was calculated. The association of failure-free survival with various prognostic clinical factors before treatment was compared (log-rank test univariate analysis). RESULTS: Failure-free survival differed significantly (P < .002) between patients with positive and patients with negative 67Ga scintigrams after one chemotherapy cycle but not at midtreatment. Failure-free survival was not significantly different between patients with positive and patients with negative CT scans at midtreatment. Twenty-two (92%) of 24 patients with negative 67Ga scintigrams after one cycle and 64 (82%) of 78 patients with negative scintigrams at midtreatment remained in complete response. In four (57%) of seven patients with positive 67Ga scintigrams after one cycle, treatment failed. CONCLUSION: 67Ga scintigraphy after one cycle of chemotherapy is a good early predictor of outcome of HD.
Adult↗
T-cell subpopulation in patients with metastatic renal cell carcinoma treated by recombinant interleukin-2, recombinant interferon-alpha, 5-fluorouracil, and vinblastine.
T-cell subpopulations were evaluated in 10 patients with metastatic renal cell carcinoma treated with recombinant interleukin-2, recombinant interferon-alpha, 5-fluorouracil, and vinblastine. T-cell subpopulation was tested by flow cytometry, and the results were compared with healthy control subjects. Mean T-cell values before treatment as compared with control were as follows: CD3, 68 vs. 73%; CD4, 34 vs. 53%; CD8, 38 vs. 31%; CD4/CD8, 1.1 vs. 1.8; CD4CD69, 20 vs. 47%, and CD8CD69, 24 vs. 19%. The difference in CD4, CD4/CD8, and CD4CD69 was statistically significant. After treatment (8 weeks), the values of CD4/CD8 ratio and CD4CD69 increased. Three patients achieved complete response, two partial response, and two had stabilization of the disease. After treatment, the CD4/CD8 ratio increased in complete responders, from 1.1 to 2.0, and CD4CD69 increased in complete and partial responders, from 11 to 37% and 23 to 31%, respectively. In nonresponders, no similar change was observed. In conclusion, increases in CD4/CD8 ratio and CD4CD69 levels in metastatic renal cell carcinoma patients may be associated with response to immunochemotherapy.
Adult↗