Our observations indicate that cardiac damage from TKI treatment is a largely underestimated phenomenon but is manageable if patients have careful cardiovascular monitoring and cardiac treatment at the first signs of myocardial damage.

The incidence and severity of oral mucositis is influenced by the type of antineoplastic treatment administered and by patient-related factors. Severe courses of oral mucositis are observed during simultaneous radiochemotherapy, which Oral Mucositis Complicating Chemotherapy and/or Radiotherapy: Options for Prevention and TreatmentWolfgang J. Köstler, MD; Michael Hejna, MD; Catharina Wenzel, MD; and Christoph C. Zielinski, MD 290 CA A Cancer Journal for Clinicians ABSTRACT Chemotherapy-and radiotherapy-induced oral mucositis represents a therapeutic challenge frequently encountered in cancer patients. This side effect causes significant morbidity and may delay the treatment plan, as well as increase therapeutic expenses.The pathogenesis of this debilitating side effect can be attributed to the direct mucosal toxicity of cytotoxic agents and ionizing radiation and to indirect mucosal damage caused by a concomitant inflammatory reaction exacerbated in the presence of neutropenia, and the emergence of bacterial, mycotic, and viral infections. affects virtually all patients with head and neck cancer who receive this therapeutic modality. 8 However, up to 40% of patients treated with conventional chemotherapy and the more than 70% of patients undergoing conditioning therapy for bone marrow transplantation also experience oral treatment-related complications. 9,10The pathogenesis of oral mucositis is not fully understood, yet it is thought to involve direct and indirect mechanisms. Direct mucosal injury by radiation and chemotherapy interfere with the average 5-to 14-day turnover time of the oral epithelium 11 and induce apoptosis. Indirect stomatotoxic effects that result from the release of inflammatory mediators, loss of protective salivary constituents, and therapyinduced neutropenia have been postulated to contribute to the development of oral mucositis and also promote the emergence of bacteria, fungi, and viruses on damaged mucosa.12 Although a linear relationship among the occurrence of oral mucositis, oral and systemic granulocyte counts, and a coincidence of resolution of mucositis with neutrophil recovery, has been demonstrated, 10,[13][14][15] significant mucositis can occur in the absence of myelotoxicity. 16,17 In addition, the prophylactic or therapeutic elimination of the pathogenic mucosal flora frequently observed in patients developing oral mucositis by various antiseptic and antimicrobial agents can at most alleviate the course of oral mucositis (see Antimicrobal Agents p. 302).Based upon these considerations, newer pathophysiologic concepts have emerged characterizing oral mucositis as having an initial inflammatory/vascular phase, an epithelial phase, a (pseudomembraneous) ulcerative/bacteriological phase and a healing phase.18 During the inflammatory phase, tissue injury induces release of free radicals, modified proteins and proinflammatory cytokines including interleukin-1β, prostaglandins and tumor necrosis factor-α (TNF-α) by epithelial, endothelial, and connective tissue cells. These ...

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Metastasis involves several distinct steps, including one in which the tumor cell, after entry into the bloodstream, comes to rest in a capillary located at the distant site where a metastatic tumor will ultimately form. Components of the blood-clotting pathway may contribute to metastasis by trapping cells in capillaries or by facilitating adherence of cells to capillary walls. Conceivably, anticoagulants could interfere with this step in the metastatic process. In this review, we have summarized current knowledge on the interaction of malignant cells, clotting factors, and anticoagulants. We used computerized (MEDLINE) and manual searches to identify studies done in humans, in animals, and in in vitro systems that were published in English between 1952 and 1998. We found many reports that the formation of metastatic tumors could be inhibited by heparin, a vitamin K antagonist (warfarin), and inhibitors of platelet aggregation (prostacyclin and dipyridamole). Despite these encouraging preliminary results and a compelling biochemical rationale, only limited information exists on the clinical use of anticoagulants for the prevention or treatment of metastatic cancer because there have been so few controlled and prospectively randomized studies on this topic. In view of the preliminary results, anticoagulants may hold promise for the prevention and treatment of metastases. We believe that larger controlled investigations are strongly warranted to evaluate the clinical potential of anticoagulants for the prevention and treatment of metastases in humans.

Analysis of results shows chemotherapy to be superior to best supportive care alone. Combination chemotherapy compared with monochemotherapy is associated with significantly higher overall (complete plus partial) response rates but nevertheless results in similar survival. ECF (epirubicin, cisplatin and 5-fluorouracil) currently represents one of the most effective regimens for advanced gastric cancer, whereas among the newer combinations, irinotecan- or taxane-based regimens have also given promising results. In patients with a poor performance status, consideration could be given to leucovorin-modulated 5-fluorouracil alone. Prognosis for the majority of patients, however, remains poor, as increases in survival were moderate at best.