Gerald P. Bodey

Causes of death in cancer patients

The records of 816 cancer patients who had a complete postmortem examination during a 3‐year period were reviewed. Death resulted from infection in 47% of the patients, from organ failure in 25%, and from infarction, hemorrhage, and carcinomatosis in 11%, 7%, and 10%, respectively. The most common fatal infections were pneumonia, septicemia, and peritonitis. The majority of infections were caused by gram‐negative bacilli, mainly E. coli, Pseudomonas spp., and Klebsiella spp. In 71% of the 816 patients, the underlying tumor precipitated the cause of death. Consequently, better modalities of cancer therapy and supportive therapy are needed.

Infection in cancer patients: A continuing association

Infection remains a major complication in patients with malignant disease. There are many factors predisposing to infection in this patient population, including local factors due to the tumor, specific deficiencies in host defense mechanisms due to certain malignant processes, and deficiencies in host defense mechanisms secondary to cancer chemotherapy. Neutropenia is probably the most important factor predisposing to infection in cancer patients. These patients require prompt broad-spectrum antibiotic therapy when fever develops. The majority of infections occurring in this patient population are caused by gram-negative bacilli and cure rates usually are between 65 and 75 percent. The most important prognostic factor is whether or not the neutrophil count recovers during the course of infection. Fungal infections have increased in frequency in neutropenic patients and often present as fevers of unknown origin. Increasingly, neutropenic patients are receiving antifungal agents as empiric therapy for persistent fever that fails to respond to antibacterial antibiotics. The most critical factor in recovery from fungal infection is remission of the underlying malignant disease.

The emergence of fungi as major hospital pathogens

During the last 25 years, substantial progress has been made in our understanding of the optimum management of fever in the immunocompromized host. The use of empirical antibiotic regimens promptly after the onset of fever in neutropenic patients led to a major reduction in the fatality rate from infection. The introduction of a multitude of new broad-spectrum antibiotics has made it possible to treat successfully a variety of bacterial infections that had been uniformly fatal. These accomplishments have resulted in prolonged survival of patients who are highly susceptible to infection. Furthermore the successful management of bacterial infections has resulted in the use of more aggressive therapy against patients’ underlying disease processes, leading to even greater susceptibility to infection. Hence, it is not surprising that fungal infections have emerged as a major cause of morbidity and mortality in immunocompromized patients.

Infections in cancer patients. Results with gentamicin sulfate therapy

Gentamicin was administered to 101 cancer patients during 122 episodes of infection. Sixty‐two (51%) infections responded. The drug was most effective for the treatment of urinary tract infection and cellulitis and ineffective against infections involving multiple body sites. Most of the infections were caused by Serratia marcescens, Pseudomonas aeruginosa, and Klebsiella sp. The response to gentamicin therapy was related to the patients neutrophil counts. Only five of the 23 (22%) infections occurring in patients with less than 100 neutrophils per mm3 responded favorably, whereas 29 of the 51 (57%) infections occurring in patients with more than 1000 neutrophils per mm3 responded favorably. Fourteen (11%) superinfections occurred while patients were receiving gentamicin. Nephrotoxicity occurred in 30% of patients with normal renal function at the onset of gentamicin therapy.

Pseudomonas Bacteremia in Patients with Malignant Diseases

During a three year period 07 cancer patients developed Pseudomonas sp. bacteremia. Fever greater than 101° was present in 97% of the patients at the onset of bacteremia. In 36 patients the lung was the site of origin. Ecthyma gangrenosum occurred in 28% of the patients. During the two week period prior to the onset of bacteremia 81% of the patients had received cancer chemotherapy and 58% had received adrenal corticosteroids. Only 14 patients (21%) recovered. The majority of the patients (69%) received a polymyxin antibiotic ns therapy for their infection and 24% of these patients recovered. Only 14% of the remaining 21 patients survived. Sixty-four percent of the patients whose absolute neutrophil count increased during the week after onset recovered compared to 8% of those whose neutrophil count decreased during that period. Polymyxin antibiotics have not improved the survival rate of patients with Pseudomonas sp. bacteremia.

Management of fever of unknown origin in patients with neoplasms and neutropenia.

During 81 febrile episodes, 76 cancer patients with neutropenia were randomly allocated to continue or discontinue antibiotics 4 days after initiation of carbenicillin and cephalothin therapy, if no infection had been demonstrated. During 56 episodes, the patients became afebrile, after initiation of antibiotics. Infection as a cause of fever was identified in 21% of the episodes. The cause of fever could not be identified in 72% of the episodes. Three of 30 patients randomized to discontinue antibiotics developed infection which ultimately caused their death. During 25 episodes, the patients remained febrile. Infection was the ultimate cause of fever in 40% of the episodes. The cause of fever could not be identified in 48%. The majority of infections documented in this group responded when gentamicin was added. Antibiotic therapy with carbenicillin and cephalothin is effective initial therapy for fever due to presumptive infection. If, after 4 days of therapy, no infection is documented and the patient is responding, the antibiotics should be continued for an additional 3 to 5 days. However, for patients not responding after the initial 4 days of therapy, the addition of gentamicin is indicated.

Antibiotic combinations for infections in neutropenic patients. Evaluation of carbenicillin plus either cephalothin or kanamycin

The combination of carbenicillin plus cephalothin (carb‐ceph) was compared to the combination of carbenicillin plus kanamycin (carb‐kan) as therapy during 179 episodes of presumed infection in 113 cancer patients with neutropenia. The overall response rate was similar for both treatment groups (48% vs. 49%). Among the episodes of identified infection, 30 of 50 (60%) responded to carb‐ceph and 28 of 48 (58%) responded to carb‐kan. In patients with persistent severe neutropenia, the response rate was better with carb‐kan than with carb‐ceph (45% vs. 15%), although the difference was not statistically significant. Neither combination was routinely effective for the treatment of infections in neutropenic patients, and no major advantages were observed with either combination.

Chemotherapy-associated oral infections in adults with solid tumors

The frequency of chemotherapy-associated oral infections in adult inpatients with solid tumors was determined in 825 subjects with carcinoma, 60 with sarcoma, and 115 with lymphoma. The total number of documented oral infections in the 1,000 patients was 97 (9.7 percent), with frequency rates of 8.4 percent, 11.7 percent, and 18.3 percent for the patients with carcinoma, sarcoma, and lymphoma, respectively. All but six of the infections were caused by a single organism. Microbiologically, 68.9 percent of the infections were ascribable to fungi, 10.7 percent to gram-negative bacilli, 10.7 percent to herpes simplex, and 9.7 percent to gram-positive cocci. The patients with solid tumors were less than one third as prone to oral infections as adults with acute leukemia treated in the same hospital. Among the solid tumor group, those with lymphoma were almost twice as likely to develop infections of the mouth during chemotherapy as those with carcinoma or sarcoma. The oral infection experience in the previously reported patients with acute leukemia and in the present series of patients with solid tumors strongly suggests that the more aggressive the malignancy and the more potent the chemotherapy, the greater the tendency to stomatologic infections.

Significance of Aspergillemia in Patients with Cancer: A 10-Year Study

The significance of blood cultures positive for Aspergillus species for patients with cancer remains unclear. The significance of aspergillemia in 36 cancer patients over a 10-year period was evaluated. True aspergillemia was rare, occurred late in the course of aspergillosis, and was seen exclusively in patients with hematologic malignancies.

Prolonged infusion of arabinosyl cytosine in childhood leukemia

Arabinosyl cytosine (ara‐C) was administered by continuous intravenous infusion to children with acute leukemia refractory to conventional chemotherapy. The dosage was 150 mg to 200 mg/M2 of body surface area per 24 hours for 5 days, repeated every 2 weeks. Forty‐six children were admitted to this study. Thirty‐four had acute lymphocytic leukemia, and 12 had acute myelocytic leukemia. Of the 34 children with acute lymphocytic leukemia, one achieved complete hematologic remission, 3 achieved good partial remission, 9 had inadequate trials of the agent, and 21 failed to show any response to this agent. Of the 12 children with acute myelocytic leukemia, 2 had complete remission, one achieved good partial remission, 5 had inadequate trials of the agent, and 4 failed to show any response. Myelosuppression was the limiting toxicity. Prolonged infusion of ara‐C probably offers no advantage over rapid intravenous injections for the induction of remissions in children with acute lymphocytic leukemia.