Acute arterial thrombosis in a patient with breast cancer after chemotherapy with 5-fluorouracil, doxorubicin, leucovorin, cyclophosphamide, and interleukin-3

Theodossiou, Christopher; Kroog, Glenn; Ettinghausen, Stephen E.; Tolcher, Anthony W.; Cowan, Kenneth H.; O’Shaughnessy, Joyce

doi:10.1002/1097-0142(19941115)74:10<2808::aid-cncr2820741011>3.0.co;2-v

Cited by 13 publications

(4 citation statements)

References 11 publications

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“…The symptoms, however, recurred despite adequate anticoagulant therapy. Arterial thrombosis associated with rhIL-3 has been reported in the literature (Theodossiou et al, 1994). No thromboembolic events were reported by Trimble et al (1993) in their paper on approximately 1000 patients treated with paclitaxel only.…”

Section: Discussionmentioning

confidence: 96%

Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer: a feasibility study

Veldhuis

Willemse²,

Beijnen³

et al. 1997

Br J Cancer

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Summary The tolerability and efficacy of four courses of paclitaxel and ifosfamide plus cisplatin every 3 weeks was evaluated in patients with residual or refractory ovarian cancer. Additionally, supportive haematological effects of recombinant human interleukin 3 (rhlL-3) and recombinant human granulocyte colony-stimulating factor (G-CSF) were studied. Paclitaxel starting dose was 135 mg m-2 (day 1), with ifosfamide dose 1.2 g m-2 day-1 (days 2-4) and cisplatin dose 30 mg m-2 day-1 (days 2-4). All 16 patients received 5.0 9g kg-1 day-' G-CSF (days 7-16) and, in addition, eight patients were randomized to receive 10 gg kg-' day-' rhlL-3 (days 5-9). Paclitaxel and ifosfamide doses were reduced when grade IV haematological toxicity occurred. In the absence of grade IV haematological toxicity and normal recovery of haematopoiesis, paclitaxel dose was escalated. Toxicity was evaluable in 56 courses, with haematological effects in 52. Despite antiemetic treatment, nausea and vomiting (2 grade 1) occurred in 50 courses. Five patients had persisting peripheral neuropathy. Renal and liver function were not affected. Grade IV neutropenia occurred in 12 out of 52 courses, with neutropenic fever in two patients, both of whom died from fatal septicaemia. Grade IV thrombocytopenia without bleeding was observed in 15 courses. Grade IV haematological toxicity was associated with hepatic metastases and concurrent increases in alkaline phosphatase (P <0.001) and gamma-glutamyltransferase (P=0.007). No relation was found between haematological toxicity and pharmacokinetic parameters of paclitaxel. Patients treated with rhlL-3 showed a tendency to a faster platelet recovery (not affecting platelet nadir), and the cisplatin dose intensity was higher (P=0.025). Six of the nine evaluable patients had a tumour response. The overall median progression-free survival was 7 months and the overall mean survival was 13 months. In conclusion, this potentially interesting combination as second-line treatment showed a low tolerability with unexpected mortality, while rhlL-3 administration tended to induce a more rapid platelet recovery.

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Section: Discussionmentioning

confidence: 96%

Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer: a feasibility study

Veldhuis

Willemse²,

Beijnen³

et al. 1997

Br J Cancer

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“…Arterial thrombotic events, including acute myocardial infarction and angina, cerebrovascular accidents, and peripheral artery thrombosis have been reported following treatment with a variety of chemotherapeutic regimens, hormonal therapy and hematopoietic growth factors (Tables 1 and 2). 7,8,17,21,24,[28][29][30][31][32][33][34][35][36][37][38][39] Cardiac risk factors were present in some cases of acute coronary syndromes, while others had no known risk factors or explanations for arterial disease. Although most of the events were temporally related to the administration of therapeutic agents, because of the very small number of events in individual studies and the lack of controlled trials, the strength of evidence for a causal relationship between cancer therapeutic agents and arterial thrombosis is provocative but weak.…”

Section: Arterial Thrombosismentioning

confidence: 99%

The Thrombophilic State Induced by Therapeutic Agents in the Cancer Patient

Lee¹,

Levine²

1999

Semin Thromb Hemost

178

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Multiple risk factors contribute to the hypercoagulable state in cancer patients. Antineoplastic therapy, including single- or multiagent chemotherapy, hormonal therapy, and hematopoietic growth factors, is an unavoidable and a significant precipitant of venous and arterial thromboses. The risk of thrombosis following cancer treatment also depends on the interaction between treatment agents, type and stage of cancer, and the presence of other risk factors for thrombosis such as advanced age, surgery, immobilization, and the use of central venous catheters. Therefore, although a causal role of cancer treatment in thrombosis is widely accepted, the pathogenic mechanisms are poorly understood and are difficult to investigate because of the multiple confounding factors that are involved. Alterations in coagulation factors, anticoagulant proteins, and endothelial damage have all been shown to occur following cytotoxic agents. The best-studied drugs with definite hypercoagulable effects are L-asparaginase and tamoxifen.

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“…Theodossiou et al demonstrated acute arterial thrombosis in a patient with stage III adenocarcinoma of the breast after chemotherapy with 5-fluorouracil, dox orubicin, leucovorin, cyclophosphamide, and interleukin-3 (IL-3), an agent used to ameliorate neutropenia in patients receiving chemotherapy, suggesting that IL-3 may be associated with increased propensity for throm bosis. 51 Little data are available about the incidence of thrombosis in breast cancer patients treated with paclitaxel or its derivatives. Sevelda et al reported about two patients who developed thrombosis after the fifth cycle of paclitaxel (175 mg/m 2 ).…”

Section: The Effect Of Chemotherapy On Blood Clotting Factors and Thementioning

confidence: 99%

Thrombophilic State in Breast Cancer

Kuhn¹,

Harbeck²,

Graeff³

1999

Semin Thromb Hemost

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Tumor cell metastasis and thrombosis are the major causes of death in cancer patients. Thrombosis in cancer patients may occur when physiologic antithrombotic systems are defective or when prothrombotic activities defeat normal physiologic antithrombotic mechanisms. Malignancies by themselves may already predispose to a hypercoagulable state in cancer patients. Tumor cells can either directly activate the blood clotting system or indirectly stimulate mononuclear cells to synthesize and express various procoagulants, subsequently leading to prothrombin activation, fibrin formation, and generation of a thrombus. In addition, other comorbid predisposing factors effecting thrombosis in cancer patients have to be considered, including surgery, bed rest, infection, long-term indwelling central venous catheters, anticoagulation, and chemotoxic or steroidal anticancer drugs used in adjuvant or palliative cancer treatment. Reliable information on the incidence of thromboembolism in cancer patients is available for breast cancer; less data have been reported for other malignancies. Chemo- and/or hormone therapy in patients with primary or metastatic breast cancer is associated with an increased thromboembolic risk, although the benefits of treatment far outweigh the risks. The current literature discussing the effect of chemo/hormone therapy on blood clotting factors and the associated risk of thrombosis is reviewed, with emphasis on new developments in the area of tissue-specific SERMs (selective estrogen receptor modulators). SERMs are employed as adjuvant therapy in primary breast cancer and in the palliation of advanced breast cancer and may be clinically useful as potential substitutes for long-term hormone replacement therapy, in the treatment of osteoporosis, and for cancer prevention therapy.

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Acute arterial thrombosis in a patient with breast cancer after chemotherapy with 5-fluorouracil, doxorubicin, leucovorin, cyclophosphamide, and interleukin-3

Cited by 13 publications

References 11 publications

Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer: a feasibility study

Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer: a feasibility study

The Thrombophilic State Induced by Therapeutic Agents in the Cancer Patient

Thrombophilic State in Breast Cancer

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