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Biomedical subjects

G P Bodey

Publications and source records attributed to G P Bodey.

At least 19 recordsLinked to original sources

Serious complications of vascular catheter-related Staphylococcus aureus bacteremia in cancer patients.

Over the period 1986 to 1989, 53 cancer patients were identified with catheter-related Staphylococcus aureus bacteremia at the University of Texas M.D. Anderson Cancer Center. Septic thrombosis was diagnosed in 12 (23%) patients and was suspected in another 3 (6%). Of the 12 patients, five developed deep-seated infections (septic emboli, endocarditis, meningitis, abscess), compared with 2 of the 38 other patients with no septic thrombosis (p < 0.01). Fever persisted for more than three days after antibiotic initiation in 52% of the patients with complications (septic thrombosis and/or deep-seated infections), compared with 19% of those without complications (p < 0.02). Of the three patients with complications who were treated for 14 days with intravenous antistaphylococcal antibiotics, two relapsed; in contrast, all of the nine patients with complications who were treated for more than 14 days (mean 4 weeks) were cured, and none relapsed (p < 0.05). Of the nine patients with complications who were treated with a long course of therapy, only one required surgery. The possibility of septic thrombosis and/or deep-seated infections should be considered in all cancer patients with catheter-related Staphylococcus aureus bacteremia, and if present, the condition should be treated with appropriate intravenous antibiotics for at least four weeks.

Adult

Azole antifungal agents.

The discovery of the antifungal activity of azole compounds represented an important therapeutic advance. Miconazole, ketoconazole, and fluconazole are currently commercially available, and itraconazole has undergone extensive clinical evaluation. Because of its limited activity and toxicity, miconazole has been replaced by newer agents. Ketoconazole has proven useful in therapy for superficial infections and invasive infections caused by the pathogenic fungi. Among its disadvantages are limited absorption in the absence of gastric acid and its potential for drug-drug interactions. Fluconazole is the only azole available as oral and intravenous preparations. Unlike other azoles, it is only minimally metabolized in the liver and largely excreted in the urine as active drug. It is more effective than ketoconazole against superficial candidal infections and is the drug of choice for maintenance therapy for cryptococcal meningitis in patients infected with human immunodeficiency virus. An advantage of itraconazole is its activity against aspergillosis. It is also active against many infections caused by pathogenic fungi. Other azole compounds are at varying stages of preclinical and clinical investigation.

Animals

In vitro activity of Ro 23-9424, a dual-action antibacterial agent, against bacterial isolates from cancer patients compared with those of other agents.

The in vitro activity of Ro 23-9424 against bacterial isolates from patients with cancer was compared with those of fleroxacin, ciprofloxacin, cefoperazone, and ceftazidime. Ro 23-9424 inhibited the majority of the members of the family Enterobacteriaceae and all Aeromonas isolates at a concentration of less than or equal to 1.0 micrograms/ml. It was also active against Acinetobacter spp. and Haemophilus influenzae, including beta-lactamase-producing strains. The MIC for 90% of isolates (MIC90) of Pseudomonas aeruginosa was 16.0 micrograms/ml. All group A and B streptococci were inhibited by less than or equal to 0.25 micrograms/ml, and 90% of group G streptococci and Streptococcus pneumoniae were inhibited by 1.0 micrograms/ml. All methicillin-susceptible strains of Staphylococcus aureus and 60% of methicillin-resistant strains were susceptible to 2.0 micrograms of Ro 23-9424 per ml, whereas the MIC90 for Staphylococcus epidermidis and Staphylococcus hominis isolates was 4.0 micrograms/ml. Staphylococcus haemolyticus and Enterococcus spp. were less susceptible; MIC90s for them were 16.0 and 32.0 micrograms/ml. Ro 23-9424 has a broad antibacterial spectrum and potential utility for therapy of infections in cancer patients.

Anti-Infective Agents

Viral pneumonia in the immunocompromised adult with neoplastic disease: the role of common community respiratory viruses.

Until recently, the viruses most often identified in lower respiratory tract infections among immunocompromised adults with neoplastic disease have been the herpesviruses (cytomegalovirus, herpes simplex virus, varicella-zoster virus, human herpesvirus-6) and adenovirus. These viral pneumonias occur with greater frequency and/or severity among these adults than among immunocompetent adults. During the last decade, mounting evidence has suggested that the RNA viruses that commonly cause lower respiratory tract disease in the general population, namely influenza virus, respiratory syncytial virus, and parainfluenza virus, are also an important cause of serious community-acquired and nosocomial lower respiratory tract disease among immunocompromised adults. Because these infections are associated with considerable morbidity and mortality and are potentially preventable and treatable, it is important that they be recognized and treated promptly. Various therapies have been tried with some reported success, including amantadine (specifically for influenza A), ribavirin, and intravenous immunoglobulin. The optimal therapy or combination of therapies for these infections among immunocompromised adults remains to be defined in controlled trials.

Adult

Ftorafur, adriamycin, cyclophosphamide and BCG in the treatment of metastatic breast cancer.

Ftorafur is a 5-fluorouracil analogue which is slowly metabolized to 5-FU, resulting in prolonged therapeutic levels of this latter drug. Ninety-one evaluable patients with metastatic breast cancer were treated with Ftorafur, Adriamycin, cyclophosphamide, and BCG (ACFTOR-BCG), in an attempt to increase the effectiveness of the program or decrease its myelosuppressive toxicity. The results of this trial were compared to those previously reported with the combination of 5-FU, Adriamycin, cyclophosphamide, and BCG (FAC-BCG). Overall objective response rates were 65% and 76% for ACFTOR-BCG and FAC-BCG, respectively. Durations of response were 12 months and 14 months for ACFTOR-BCG and FAC-BCG (p = 0.53). The median survival of responders was 22 and 23.9 months, respectively. Substantial toxicity was observed with Ftorafur: nausea and vomiting severe enough to cause weight loss was observed in a substantially higher fraction of the patients treated with this drug than with 5-FU. Other side-effects, which were not observed with the 5-FU combination, were somnolence, dizziness, personality changes, tremor, ataxia, and confusion. No differences in myelosuppressive toxicity were observed between the two combinations, and the incidence of infectious complications was identical. The combination of Ftorafur, Adriamycin, cyclophosphamide and BCG did not offer any advantages with respect to increased effectiveness or reduced toxicity over the FAC-BCG regimen in breast carcinoma.

Adult

Treatment of acute leukemia in protected environment units.

Thirty evaluable patients with acute leukemia (AL), aged 14 to 48-year-old received remission induction chemotherapy on a protected environment-prophylactic antibiotic program. Twenty-seven (90%) of these patients achieved complete remission and 17 remained in complete remission for 1 to 22 months. Although these patients spent 36% of their time with neutrophil counts less than 100/mm3, they spent only 20% of their time with fever. Major infection was present during only 7% of the days when neutrophil count was less than 100/mm3. No patient died of an infectious complication during remission induction therapy.

Adolescent

Neocarzinostatin: a phase I clinical trial with five-day intermittent and continuous infusions.

Neocarzinostatin, a polypeptide antibiotic, was administered by both continuous and intermittent intravenous infusion to 76 patients with a variety of malignant diseases. Doses ranged from 500 to 6500 units/m2 X 5 days. With levels greater than or equal to 1800 units/m2, bone marrow suppression (particularly thrombocytopenia) was the dose-limiting toxicity. Delayed bone marrow recovery was less dose-dependent and occurred in 58% of initial treatment courses in solid tumor patients. Allergic reactions were more frequent with intermittent than with continuous infusions (20% vs. 2% of courses). No complete or partial remissions were observed among solid tumor patients although clinical improvement was noted in one patient with mycosis fungoides and one patient with multiple myeloma. One complete and two partial remissions were noted among 21 patients with acute leukemia. There was one complete remission in a patient with chronic leukemia. Leukemic patients on intermittent therapy evidenced greater change in bone marrow cellularity than those treated by continuous infusion. Although neocarzinostatin has some activity in the treatment of acute leukemia, continuous infusion offers no advantage over intermittent therapy.

Antibiotics, Antineoplastic

Nodular malignant lymphomas: factors affecting complete response rate and survival.

The records of 109 patients with non-Hodgkin's lymphoma of nodular pattern were reviewed to determine which factors were associated with a favorable response to therapy and prolonged survival. A logistic regression model was utilized to identify the pertinent variables. Prognostic factors associated with a favorable response were, in order of decreasing importance: treatment with an Adriamycin combination regimen, absence of bulky tumor, and no exposure to prior chemotherapy. Thos associated with prolonged survival were: normal hemoglobin level, treatment with an Adriamycin combination regimen, female sex, and no prior exposure to therapy. Achievement of complete remission in these disorders resulted in a statistically longer duration of survival compared to partial responses or failures. Patients whose complete remission was induced with an Adriamycin-containing regimen and maintained with BCG immunotherapy had a significantly longer complete remission than those who did not receive BCG. Knowledge of these factors can be important in planning and analyzing future therapeutic trials.

Antineoplastic Agents

Adriamycin, BCNU, ftorafur chemotherapy of pancreatic and biliary tract cancer.

Twenty-six evaluable patients with disseminated or locally unresectable pancreatic or biliary tract carcinoma received Ftorafur (4 g/m2 iv day 1 and 22 and 2 g/m2 iv day 4 and 26), Adriamycin (60 mg/m1 IV day 1 and 45 mg/m2 iv day 22) and BCNU (150 MG/M2 IV DAY 1) combination chemotherapy (FAB) repeated at 6--8 week intervals. Two (29%) complete and one (14%) partial remissions were observed in 7 patients with biliary carcinoma while 5 of 19 (26%) patients with pancreatic carcinoma achieved partial remissions. Median survival for responding patients was approximately 11 months (range 7--16+) with median survivals of about 6 months (p less than 0.05 and about 3 months (p less than 0.05) for patients with stable and progressive disease. Major drug toxicity was myelosuppression with median lowest granulocyte counts of 1,000/microliters and platelet counts of 88,000/microliters. Approximately 25% of patients required antibiotic therapy for fever of unknown origin or documented infections. Other tolerable drug toxicities included nausea, vomiting and mucositis. The FAB regimen appears quite promising in biliary tract cancer and has efficacy in pancreatic carcinoma that warrants further clinical trials. Because of myelotoxicity observed with this regimen we now recommend a BCNU starting dose of 100 mg/m2 instead of 150 mg/m2.

Adult

Chemoimmunotherapy with or without oophorectomy in premenopausal patients with advanced breast cancer.

Ninety-eight premenopausal patients with stage IV breast cancer were treated with chemoimmunotherapy alone, or with combination oophorectomy-chemoimmunotherapy either simultaneously (chemoimmunotherapy within four weeks of oophorectomy) or sequentially (delayed chemoimmunotherapy until evidence of progressive disease or no response to oophorectomy). The chemoimmunotherapy consisted of a three-drug combination of Adriamycin, cyclophosphamide, and 5-fluorouracil or Ftorafur; immunotherapy consisted of either oral levamisole, BCG by scarification, or a combination of both. Forty patients underwent simultaneous oophorectomy-chemoimmunotherapy, with a response rate of 85% and a median duration of response of 25 months. Response rate of 69% and a median duration of response of 16.6 months was observed with the 29 patients who received sequential oophorectomy-chemoimmunotherapy. Another 29 patients were treated with chemoimmunotherapy alone and achieved a response rate of 87% and a median duration of response of 11.8 months. Though there were no significant differences in the response rate, patients treated with chemoimmunotherapy alone had a significantly shorter median duration of response (P less than 0.05). This would suggest that oophorectomy in combination with chemoimmunotherapy is the most favorable treatment modality for premenopausal patients with advanced metastatic breast cancer.

BCG Vaccine

Phase II evaluation of vindesine in the treatment of colorectal and esophageal tumors.

A phase II study of vindesine was carried out in 33 patients with colorectal cancer and nine patients with esophageal cancer. With the exception of six previously untreated patients with esophageal cancer, all others were refractory to 5-FU-containing regimens, w,hich included vincristine in ten patients. The initial dose of vindesine was 4 mg/m2 administered intravenously over 30 min every 2 weeks. Tumor regression less than 50% was set patients (six colorectal and two esophageal) achieved minor responses. Prior treatment with vincristine did not seem to influence response to vindesine. In general, the treatment with vindesine was well tolerated. The hematologic toxicity was acceptable and manifested mainly as moderate and transient neutropenia. The major nonhematologic toxicity was peripheral neuropathy, which became limiting. It occurred in 33% of patients who received two or more courses of vindesine. Because of the apparent antitumor activity and dose-limiting neurotoxicity of vindesine in this sutdy, further investigations of this compound should be conducted in combination chemotherapy programs for patients with metastatic gastrointestinal cancers.

Adult

A randomized study of carbenicillin plus cefamandole or tobramycin in the treatment of febrile episodes in cancer patients.

Patients were randomly assigned to receive carbenicillin plus tobramycin by continuous infusion (C+T), carbenicillin plus cefamandole by continuous infusion (C+CC) or carbenicillin plus cefamandole by intermittent infusion (C+IC) during 490 febrile episodes. Carbenicillin was administered over 2 hours every 4 hours. The per cent of cures achieved during the 235 documented infections was 65 per cent for C+CC, 57 per cent for C+IC and 54 per cent for C+T. Among those infections caused by single gram-negative bacilli, C+CC produced a higher cure rate than C+IC or C+T(74 per cent versus 59 per cent versus 50 per cent). C+CC was significantly more effective than C+IC among patients with persistent severe neutropenia of less than 100 neutrophils/mm3 (65 per cent versus 21 per cent, p = 0.03). If the infecting organism was sensitive to both antibiotics, the cure rate which occurred during 12 per cent to 13 per cent of the febrile episodes, regardless of antibiotic regimen. However, it occurred significantly more often during documented infections than during fevers of unknown etiology (20 per cent versus 6 per cent, p less than 0.001). C+CC appears to be the most effective of the three regimens for the treatment of infections in patients with persistent severe neutropenia.

Bacterial Infections

Necrotizing colitis in patients with cancer.

Necrotizing lesions of the colon occur in patients with malignancy. We identified 26 patients with cancer (23 with acute leukemia and three with solid tumors) who died from necrotizing colitis. Autopsies revealed three pathologic categories: pseudomembranous colitis in 69 per cent, agranulocytic colitis in 19 per cent and ischemic colitis in 12 per cent. Most died from sepsis. A comparison of characteristics was made with a control population matched for diagnosis, age, cause of death and duration of neoplasia. Nearly all patients in both groups had fever and were granulocytopenic secondary to chemotherapy. Most received antineoplastic and antimicrobial regimens during the month prior to their terminal illness. Abdominal pain and distention, stomatitis and necrotizing pharyngitis were frequently associated with colitis. Hyperbilirubinemia was a frequent late complication in those with colitis and the control group. Single and multiorganism septicemia were found more frequently in patients with colitis. As antemortem diagnosis was unusual, aggressive attempts at diagnosis are necessary to assess the true incidence of this disorder and the best therapy.

Adolescent

Protected environment-prophylactic antibiotic program for malignant lymphoma. Randomized trial during chemotherapy to induce remission.

Fifty-eight patients with malignant lymphoma were randomly allocated to receive three courses of chemotherapy to induce remission with CHOP-Bleo on the protected environment-prophylactic antibiotic (PEPA) program (30 patients) or as controls (28 patients). The complete remission rate for all patients was 74 per cent, for patients with diffuse histiocytic lymphoma 78 per cent and for patients with nodular poorly differentiated lymphocytic lymphoma 65 per cent. There were no significant differences in response rates and duration of responses between those on the PEPA program and control patients. The frequency of infection was significantly lower among the patients on the PEPA program, and dosage escalation of the chemotherapeutic agents was accomplished more often among these patients. Dosage escalation did not increase the complete remission rate, but it did reduce the relapse rate and signficantly reduced the fatality rate. The duration of remission and survival was significantly longer for those patients who received dosage escalation.

Adolescent

Unusual mucocutaneous infections in immunosuppressed patients with leukemia.

Patients with leukemia may become severely infected with usually nonpathogenic organisms and are also prey to infection in unusual sites and by unusual organisms.. Every organism isolated from such a patient must be considered a potential enemy, regardless of its pathogenic reputation, and evidence of infection must be sought.

Anti-Infective Agents

A randomized comparative trial of three aminoglycosides--comparison of continuous infusions of gentamicin, amikacin and sisomicin combined with carbenicillin in the treatment of infections in neutropenic patients with malignancies.

Continuous infusions of gentamicin, amikacin or sisomicin combined with carbenicillin were compared in a randomized study in the treatment of 572 febrile episodes in 281 patients with cancer. The three treatments (C+A, C+A and C+S) were equally effective with no significant differences in response rate overall (67%, 68%, 67%) or in any infection, except septicemia where C+G had a significantly lower response rate than the other two groups. Pneumonia, the most common infection, had the lowest response rate for all three groups (45-50%). Klebsiella spp. were the most common pathogens and showed a lower response rate than other gram-negative bacilli (P = 0.003). Patients with persistent severe neutropenia had a response rate of 56%. Azotemia was significantly less common in patients with documented infection treated with C+A than in the C+S group. Combinations of carbenicillin plus an aminoglycoside antibiotic are effective for the treatment of infections in neutropenic patients.

Adolescent