Administration Of Chemotherapy In Patients Research Articles

Hemolysis and Methemoglobinemia Secondary to Rasburicase Administration

To report a case of hemolytic anemia and methemoglobinemia developing after rasburicase administration to a patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency. A 50-year-old African American man was hospitalized with new onset seizure, diabetic ketoacidosis, respiratory failure, and acute renal failure. Serum uric acid concentrations were elevated, and the patient was treated with one dose of intravenous rasburicase 22.5 mg for acute renal failure secondary to hyperuricemia. Routine arterial blood gas analyses performed after rasburicase was administered revealed elevated methemoglobin concentrations, which peaked at 14.7%. Hemolytic anemia developed as evidenced by a fall in blood hemoglobin from 14.8 to 5.3 g/dL. The patient made a full recovery following aggressive fluid therapy, blood transfusions, and respiratory support. G6PD deficiency was subsequently confirmed. The Naranjo probability scale indicated that rasburicase was a probable cause of hemolytic anemia and methemoglobinemia. Rasburicase is contraindicated in patients with G6PD deficiency as it may cause hemolytic anemia and methemoglobinemia. As of September 26, 2005, simultaneous occurrence of hemolytic anemia and methemoglobinemia has not been reported in patients receiving rasburicase. As of September 26, 2005, screening for G6PD deficiency should be performed whenever possible prior to chemotherapy administration in patients at risk of developing tumor lysis syndrome.

Patient Subsets Benefiting from Adjuvant Therapy Following Surgical Resection of Non–Small Cell Lung Cancer

Adjuvant chemotherapy is the standard of therapy for some patients with stages I, II, and III breast and colon cancer. The therapeutic efficacy of adjuvant chemotherapy following surgical resection of early stage non-small cell lung cancer (NSCLC) has been less clear. A meta-analysis was reported in 1995 of patients who underwent surgical resection for early stage NSCLC and were then randomized to either observation or chemotherapy. This meta-analysis showed a 13% reduction in the hazard ratio of death, leading to a 5% absolute improvement in survival 5 years after the start of adjuvant cisplatin-based chemotherapy treatment compared with observation only. Multiple prospective randomized trials for patients with NSCLC were planned and undertaken to attempt to validate the observations of the meta-analysis. Six trials with > or =150 patients with early stage NSCLC (stages I-IIIA) on each arm have been reported in the last 2 years. Four of the six trials show a survival advantage for the patients with early stage NSCLC treated with adjuvant chemotherapy compared with those who underwent observation. The survival benefit in these four studies varies from a 4% to a 16% survival advantage at 4 to 5 years after the start of chemotherapy. The hazard ratio of death for the patients treated with chemotherapy ranged from 0.61 to 0.86 compared with patients on observation. Thus, the information available at the current time supports the administration of chemotherapy for patients with stages IB and II NSCLC. Further research will be needed to define the role of adjuvant chemotherapy and its use in conjunction with chest radiotherapy for the treatment of patients with resected stages IA and IIIA NSCLC.

Pharmacokinetics Following Intraventricular Administration of Chemotherapy in Patients with Neoplastic Meningitis

Intraventricular administration of chemotherapy is one approach to overcoming the limited distribution of anticancer drugs and their active metabolites into the CNS. This form of regional chemotherapy has led to effective treatment of occult and overt meningeal leukaemia in humans. In contrast, the efficacy of this therapy is extremely limited in the treatment of leptomeningeal dissemination of various solid tumours. Pharmacokinetic studies of the commonly intraventricularly applied anticancer agents in humans have demonstrated that, using low drug doses, very high drug concentrations can be achieved in the cerebrospinal fluid (CSF) and relatively high concentrations in the leptomeninges but not in the brain tissue and the plasma. Therefore, this approach is not an effective treatment for bulky disease of brain tissue, and results in minimal systemic toxicity. In comparison with intralumbar administration, lower interpatient variability of CSF drug concentrations and improved clinical efficacy were observed. 'Concentration x time' schedules, i.e. frequent small drug doses over a short period, enable long-term CSF exposure to cytotoxic drug concentrations while avoiding excessively high and potentially neurotoxic drug concentrations. The technique of ventriculolumbar cerebrospinal perfusion delivers continuously high drug concentrations throughout the CSF for several hours, but its widespread use is limited by the technical complexities of this approach. In this article, the dosages, schedules and pharmacokinetic data of routinely used intraventricular agents in humans, e.g. methotrexate, cytarabine, glucocorticoids and thiotepa, are outlined in detail. In addition, pharmacokinetic data of investigational agents for intraventricular administration (diaziquone, DTC 101, mercaptopurine, mafosfamide, etoposide, topotecan, nimustine [ACNU] and bleomycin) are presented. Better understanding of the CSF pharmacology of these drugs is an essential prerequisite for safe, effective administration of these drugs. Investigational efforts are underway to verify the feasibility and efficacy of different dosages, schedules and combination therapies of these new intra-CSF agents. Current and future clinical research should also focus on methods allowing the delivery of tumoricidal drug concentrations for extended periods into the CSF and the brain tissue while minimising neurotoxicity and systemic toxicity (e.g. liposomal drug preparations, monoclonal antibodies, immunotoxins and gene therapy).

Response to chemotherapy, quality of life benefits and survival in advanced non-small cell lung cancer: review of literature results

The survival benefit obtained with chemotherapy administration in advanced non-small cell lung cancer (NSCLC) patients has been demonstrated by numerous meta-analyses published between 1993 and 1999 on randomised trials comparing best supportive care with or without chemotherapy. However, some clinicians are still reluctant to prescribe chemotherapy in these patients, arguing that the benefit is too small to counterbalance the side effects. The goal of this paper is to review the reasons favouring the administration of chemotherapy. First, there is a demonstrated relationship between response to chemotherapy and survival, although more data are needed to assess response to chemotherapy as a surrogate for survival. Secondly, recent randomised trials comparing best supportive care to chemotherapy, but not included in the meta-analyses, have successfully incorporated quality of life (QoL) as an endpoint, sometimes as a primary endpoint. The survival benefit shown by the meta-analyses is confirmed by these latter trials; in addition, the QoL assessments, despite some methodological problems inherent to attrition in these poor prognosis patients, also favour chemotherapy with regard to some global aspects, such as physical, functioning, emotional, cognitive or social components, as well as some lung cancer symptoms. We conclude that there are no longer convincing arguments against chemotherapy administration in patients with advanced NSCLC, at least in patients eligible for inclusion in clinical trials.

Thermo–Chemotherapy and Electromotive Drug Administration of Mitomycin C in Superficial Bladder Cancer Eradication

Objective: To assess the feasibility and safety of two novel methods for intravesical chemotherapy administration in patients suffering from superficial bladder carcinomas. To draw preliminary considerations concerning the ablative effect on marker lesion using novel approaches compared to standard intravesical chemotherapy. Methods: Eighty patients suffering from single, recurrent, low–stage, low–grade superficial bladder tumor entered a prospective nonrandomized study. Thirty–six of them were treated by means of mitomycin C instillation as a standard procedure. In 29 patients mitomycin C solution was administered in combination with local microwave–induced hyperthermia and in 15 patients the mitomycin C solution was administered according to the electromotive drug procedure. The treatment was scheduled as a short term neo–adjuvant regimen prior to transurethral resection. Feasibility and safety of the different procedures were evaluated on an outpatients basis. The local toxicity induced by different approaches was defined and compared using a subjective questionnaire. Results: Both intravesical chemotherapy administered in combination with hyperthermia and according to the electromotive drug technique appeared to be feasible and safe. Local toxicity induced by thermo–chemotherapy was more severe than that registered for electromotive drug technique and standard intravesical chemotherapy. Local toxicity was always short and self healing without early or delayed major complications. A higher complete response rate on marker lesion was observed after thermo–chemotherapy compared to other administration methods. Conclusion: The intravesical administration of mitomycin C can be safely performed in the form of both thermo–chemotherapy and electromotive drug approach with an increased ablative success rate on small superficial tumor involving only minimal local side effects.

Mediastinal Masses Diagnosed as Thymus Hyperplasia by Fine Needle Aspiration Cytology

Thymic hyperplasia in the anterior mediastinum can occur in healthy children as idiopathic thymic hyperplasia or as a rebound effect after administration of chemotherapy in patients with malignancies. Thymic hyperplasia after chemotherapy is a well-documented phenomenon, particularly in children and less frequently in adults. Both forms of thymic hyperplasia are a diagnostic challenge, and most patients undergo surgical exploration. Fine needle aspiration cytology (FNAC) has supposed to be inadequate to diagnose benign thymic hyperplasia and to separate it from malignant disease. We report the cytologic findings on eight patients presenting with a mass in the anterior mediastinum that was diagnosed as thymic hyperplasia on FNAC. In five patients the masses developed after chemotherapy. The remaining three patients were healthy children. Three patients underwent ultrasound-guided aspiration; in five cases the procedure was performed under computerized guidance. In all eight patients the cytologic smears showed a mixed population of lymphoid cells. Cytologic diagnosis of thymic hyperplasia was confirmed by immunophenotyping in three patients and by follow-up studies in all of them (median, 68 months; range, 8-113). In contrast to previous reports, this study demonstrated the utility of FNAC as a front-line investigative procedure in diagnosing thymic hyperplasia.

Decision making for chemotherapy administration in patients with low risk gestational trophoblastic neoplasia

The thrust in the management of low risk gestational trophoblastic neoplasia (GTN) has been to find the most effective agent with the least toxicity that causes the least disruption of the patient9s activities. We have studied biweekly actinomycin-D 1.25 mg M-2 (pulsed act-D, 18 evaluable patients) to determine whether it has the same primary efficacy rate as the 5-day course of actinomycin-D 12 mcg kg-1 (5-day act-D, 43 evaluable patients) in low risk GTN. The primary cure rate was 88.4% for the 5-day act-D group and 77.8% for the pulsed act-D group. The data appear to show a therapeutic advantage for the use of the 5-day regimen. However, the difference between 22.2% failure for pulsed act-D and 11.6% failure for the 5-day act-D is not statistically significant; P=0.45(Fisher9s exact test, two tails). Many studies, both of act-D and of methotrexate, may be invalid because the criteria for diagnosing GTN are not sufficiently stringent, yet all our current practice is based on the reported literature. The data from the present study illustrates the difficulties of drawing valid conclusions from the information available in the literature. Before assuming that less drug for less time is the best procedure a prospective randomized study embodying stringent diagnostic criteria and uniform patient attributes appears to be indicated.

Decision making for chemotherapy administration in patients with low risk gestational trophoblastic neoplasia

The thrust in the management of low risk gestational trophoblastic neoplasia (GTN) has been to find the most effective agent with the least toxicity that causes the least disruption of the patient's activities. We have studied biweekly actinomycin-D 1.25 mg M-2(pulsed act-D, 18 evaluable patients) to determine whether it has the same primary efficacy rate as the 5-day course of actinomycin-D 12 mcg kg-1(5-day act-D, 43 evaluable patients) in low risk GTN. The primary cure rate was 88.4% for the 5-day act-D group and 77.8% for the pulsed act-D group. The data appear to show a therapeutic advantage for the use of the 5-day regimen. However, the difference between 22.2% failure for pulsed act-D and 11.6% failure for the 5-day act-D is not statistically significant;P=0.45(Fisher's exact test, two tails). Many studies, both of act-D and of methotrexate, may be invalid because the criteria for diagnosing GTN are not sufficiently stringent, yet all our current practice is based on the reported literature. The data from the present study illustrates the difficulties of drawing valid conclusions from the information available in the literature. Before assuming that less drug for less time is the best procedure a prospective randomized study embodying stringent diagnostic criteria and uniform patient attributes appears to be indicated.

Clinical Utility of Calculated Creatinine Clearance as a Guide to Chemotherapy in Patients with Gynecologic Malignancies*

To examine the relationship between calculated and measured creatinine clearance, and also to evaluate the clinical utility of calculated creatinine clearance before administration of chemotherapy in patients with gynecologic malignancies. In 38 patients with gynecologic malignancies, a total-69 paired creatinine clearance measured by 24-hour urinary creatinine clearance and calculated were compared. The significant correlation (r = 0.597, p < 0.0001) was observed between creatinine clearances determined by both methods. There were 26 (37.7%) 24-hour urine collections. The correlation between two methods improved when these inaccurate samples were excluded (r = 0.876, p < 0.0001). In addition, if a creatinine clearance of 50 ml/min is set as a threshold for dose modification, only 2.9% of the patients would have received reduced doses inappropriately, by using the calculated creatinine clearance alone. These results suggest that in patients with gynecologic malignancies, a calculated creatinine clearance prior to chemotherapy is sufficient for evaluation of renal function and measured creatinine clearance would be determined only when calculated creatinine clearance is below the threshold for dose modification.

Hypersensitivity Reactions to Chemotherapy Agents in Patients Receiving Chemoimmunotherapy With High-Dose Interleukin 2

Treatment with the immune system modulator interleukin 2 (IL-2) can result in a number of immunologic abnormalities ranging from suppression of delayed-type hypersensitivity responses and neutrophil activity to autoimmune thyroiditis and hypersensitivity reactions against iodine-containing radiographic contrast media. There are a number of published reports of chemoimmunotherapy using IL-2 in combination with various chemotherapeutic agents to treat patients with certain cancers, but none have described hypersensitivity responses to the chemotherapeutic agents given. In the early stages of an ongoing clinical trial of the efficacy of combination chemoimmunotherapy for the treatment of patients with metastatic melanoma, we discovered that a number of the patients experienced unexpected hypersensitivity reactions after receiving chemotherapy. We therefore decided to examine these hypersensitivity reactions in detail. During the period of March 1993 through February 1994, 31 patients with metastatic melanoma were treated either by chemotherapy (dacarbazine, cisplatin, and tamoxifen) or by chemoimmunotherapy (the same drug regimen plus interferon alfa and high-dose IL-2). Twelve patients were treated in a non-randomized pilot study, with six receiving chemotherapy and six receiving chemoimmunotherapy. The six patients who received chemotherapy also received carmustine (BCNU). Nineteen subsequent patients were treated in a prospective, randomized study to compare the two therapeutic approaches. In total, 15 of the 31 patients were treated by chemotherapy alone, and 16 were treated by combination chemoimmunotherapy. Overall, the patients in the two groups were balanced in terms of age, sex, and stage of disease. Ten of 16 chemoimmunotherapy patients exhibited type I hypersensitivity reactions during chemotherapy administration, ranging from pruritus, erythema, and edema to hypotension with hemodynamic instability that required pressor therapy. None of the 15 patients on the chemotherapy regimen exhibited hypersensitivity reactions. All patients in the chemoimmunotherapy group gained weight and had elevated white blood cell and eosinophil counts during chemotherapy; these effects were more prominent in those with hypersensitivity reactions. Hypersensitivity reactions occurred within several hours after chemotherapy administration in patients who had previously received one to two cycles of high-dose IL-2, suggesting that prior IL-2 therapy sensitized patients to cisplatin or dacarbazine. This is the first report of IL-2-induced hypersensitivity to chemotherapy agents.

Subclinical Hepatic Toxicity During Combination Chemotherapy for Breast Cancer

We evaluated serial liver function tests (LFT) and serial liver imaging procedures for 190 consecutive patients with breast carcinoma to assess the incidence and severity of hepatic abnormalities during treatment with combination chemotherapy. Thirty-four percent of patients receiving adjuvant chemotherapy and 52% of patients being treated for metastatic breast cancer had one or more LFT abnormalities before initiation of therapy. Among patients with normal baseline LFT results, 77% of those receiving adjuvant chemotherapy and 82% being treated for metastatic breast cancer developed LFT abnormalities during therapy. Liver function test abnormalities were mild to moderate and never led to interruption of treatment; they appeared within the first three months of chemotherapy and normalized in 90% within one year of cessation of treatment. Our analysis suggests that LFT abnormalities detected during the administration of chemotherapy for patients with breast cancer are a manifestation of drug toxicity and that such abnormalities are insufficient evidence of hepatic metastases.