Cytostatic antibiotics of the anthracycline class are the best known of the chemotherapeutic agents that cause cardiotoxicity. Alkylating agents such as cyclophosphamide, ifosfamide, cisplatin, carmustine, busulfan, chlormethine and mitomycin have also been associated with cardiotoxicity. Other agents that may induce a cardiac event include paclitaxel, etoposide, teniposide, the vinca alkaloids, fluorouracil, cytarabine, amsacrine, cladribine, asparaginase, tretinoin and pentostatin. Cardiotoxicity is rare with some agents, but may occur in >20% of patients treated with doxorubicin, daunorubicin or fluorouracil. Cardiac events may include mild blood pressure changes, thrombosis, electrocardiographic changes, arrhythmias, myocarditis, pericarditis, myocardial infarction, cardiomyopathy, cardiac failure (left ventricular failure) and congestive heart failure. These may occur during or shortly after treatment, within days or weeks after treatment, or may not be apparent until months, and sometimes years, after completion of chemotherapy. A number of risk factors may predispose a patient to cardiotoxicity. These are: cumulative dose (anthracyclines, mitomycin); total dose administered during a day or a course (cyclophosphamide, ifosfamide, carmustine, fluorouracil, cytarabine); rate of administration (anthracyclines, fluorouracil); schedule of administration (anthracyclines); mediastinal radiation; age; female gender; concurrent administration of cardiotoxic agents; prior anthracycline chemotherapy; history of or pre-existing cardiovascular disorders; and electrolyte imbalances such as hypokalaemia and hypomagnesaemia. The potential for cardiotoxicity should be recognised before therapy is initiated. Patients should be screened for risk factors, and an attempt to modify them should be made. Monitoring for cardiac events and their treatment will usually depend on the signs and symptoms anticipated and exhibited. Patients may be asymptomatic, with the only manifestation being electrocardiographic changes. Continuous cardiac monitoring, baseline and regular electrocardiographic and echocardiographic studies, radionuclide angiography and measurement of serum electrolytes and cardiac enzymes may be considered in patients with risk factors or those with a history of cardiotoxicity. Treatment of most cardiac events induced by chemotherapy is symptomatic. Agents that can be used prophylactically are few, although dexrazoxane, a cardioprotective agent specific for anthracycline chemotherapy, has been approved by the US Food and Drug Administration. Cardiotoxicity can be prevented by screening and modifying risk factors, aggressively monitoring for signs and symptoms as chemotherapy is administered, and continuing follow-up after completion of a course or the entire treatment. Prompt measures such as discontinuation or modification of chemotherapy or use of appropriate drug therapy should be initiated on the basis of changes in monitoring parameters before the patient exhibits signs and symptoms of cardiotoxicity.

Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention.

Toxicity of the respiratory system is a common side effect and complication of anticancer therapy that can result in significant morbidity. The range of respiratory compromise can extend from acute lethal events to degrees of chronic pulmonary decompensation, manifesting years after the initial cancer therapy. This review examines the anatomic-histologic background of the lung and the normal functional anatomic unit. The pathophysiology of radiation and chemotherapy induced lung injury is discussed as well as the associated clinical syndromes. Radiation tolerance doses and volumes are assessed in addition to chemotherapy tolerance and risk factors and radiation-chemotherapy interactions. There are a variety of measurable endpoints for detection and screening. Because of the wide range of available quantitative tests, it would seem that the measurement of impaired lung function is possible. The development of staging systems for acute and late toxicity is discussed and a new staging system for Late Effects in Normal Tissues (LENT) is proposed.

Injury to the lung from cancer therapy: Clinical syndromes, measurable endpoints, and potential scoring systems

Between 1972 and 1989, the incidence of viridans streptococcal bacteremia at the University of Texas M D Anderson Cancer Center in Houston increased from one case per 10,000 admissions to 47 cases per 10,000 admissions (P less than 0001) A shock syndrome characterized by hypotension, rash, palmar desquamation, adult respiratory distress syndrome, and occasionally death developed in 26% of cases of streptococcal septicemia but in only 4% of cases of septicemia involving other gram-positive bacteria (P = 0005) The risk of streptococcal infection increased with the prophylactic administration of trimethoprim-sulfamethoxazole or a fluoroquinolone (P less than 0001) and with profound neutropenia (P less than 0001) Treatment of chemotherapy-induced gastritis with antacids or with histamine type 2 (H2) antagonists was associated with a sevenfold increase in risk (P less than 001), while sucralfate therapy did not increase risk (P = 65) Streptococcal infection may result from gastric overgrowth of organisms resistant to trimethoprim-sulfamethoxazole in an antacid- or H2 antagonist-induced alkaline environment, with the gastrointestinal tract ulceration caused by antineoplastic therapy providing a convenient portal of entry In patients receiving chemotherapy, replacement of antacids or H2 antagonists by an acid-sparing regimen should be considered to preserve the natural acidic barrier to infection

Septicemia and Shock Syndrome Due to Viridans Streptococci: A Case-Control Study of Predisposing Factors

https://www.amjmed.com/article/0002-9343(94)90009-4/pdf

Bacteremia due to viridans streptococci in neutropenic patients: A review

Between 1988 and 1991, 26 episodes of bacteremia due to viridans streptococci occurred in 25 neutropenic patients undergoing intensive chemotherapy for hematologic malignancies. Complications related to the bacteremia were observed in 10 episodes: unilateral pulmonary infiltrates (4), acute respiratory distress syndrome (ARDS) (4), hypotension (3), and endocarditis (2). All patients with ARDS had received high doses of cytosine arabinoside and had bacteremia due to Streptococcus mitis. Death occurred in three patients (12%) but was possibly related to bacteremia in only one case. Case patients who had received prophylaxis with quinolones were compared with matched control patients who received similar prophylaxis but who did not have bacteremia due to viridans streptococci. Multivariate analysis of predisposing factors showed that high doses of cytosine arabinoside (P = .01), the presence of mucositis (P = .02), and the absence of previous therapy with parenteral antibiotics (P = .01) were independent risk factors for the development of viridans streptococcal bacteremia. Of 259 patients who had received quinolone prophylaxis during the study period, 22 (8.5%) developed an episode of viridans streptococcal bacteremia as compared with three episodes (3.7%) in 82 patients who had received a quinolone and penicillin (P = .07). However, the latter three episodes were caused by strains with decreased susceptibility to penicillin, thus suggesting that resistance to penicillin might limit the use of this antibiotic as a prophylactic agent in the future.

/pdf/bacteremia-due-to-viridans-streptococcus-in-neutropenic-2kkwp31asx.pdf

Bacteremia Due to Viridans Streptococcus in Neutropenic Patients with Cancer: Clinical Spectrum and Risk Factors

Seventy-four adult patients with acute leukemia in relapse were studied. They received high-dose intravenous boluses of cytosine arabinoside (Ara-C) according to the following schedules: 3 g/m2 over 2 hours, every 12 hours for 4 to 12 consecutive doses, or a continuous infusion over 5 days at 200, 400, or 800 mg/m2/day. The patients' ages ranged from 16 to 68 years (median, 35). Subacute pulmonary failure attributable to Ara-C was observed in 16 of 72 evaluable patients (22%) and appeared 2 to 21 days (median, 6) after the first dose. None of the 28 patients who received up to six doses experienced any toxicity. With repeated courses or more than six doses in the first course there was a sharp increase in the incidence of toxicity. Thus, subacute pulmonary failure developed in 6 of 24 patients who received 9 doses and 6 of 19 patients who received 12 doses. The increase in toxicity with increasing number of doses is significant (P = 0.03). This suggests that the high-dose Ara-C regimen should be used with awareness of possible drug-induced pulmonary toxicity.

Brad M. Cogan

Papers

Subacute pulmonary failure complicating therapy with high-dose ara-C in acute leukemia