Reversible Renal Impairment Research Articles

Pain Management in Patients with Hepatorenal Syndrome: A Literature Review

Introduction: Patients with cirrhosis often present with pain as a common complaint. Pharmacological pain management safety depends on the excretion and metabolism of drugs by the kidney and the liver. The analgesic choice in cirrhotic patients can be tremendously challenging, especially in patients with hepatorenal syndrome, a potentially reversible renal impairment associated with an increased drug accumulation and a high risk of potential toxicity. Choice and dose of medications depend on various factors, including the severity of the condition, possible drug interactions, drug dependence, and liver transplant status. Ideally, medications should be titrated from the lowest effective dose to higher strength. This review aims to discuss the pharmacodynamic and pharmacokinetics of analgesics used in cirrhotic patients. The metabolism of each drug, route of administration, pathophysiology, and limitations of their use are discussed to better understand their implementation in patients with cirrhosis and HRS. For this purpose, we performed a systematic literature search in PubMed and Google Scholar. Articles were searched via search terms and keywords. Certain high potency opioids like Sufentanil, Fentanyl, Remifentanil, Oxymorphone, and Butorphanol can be used cautiously. Low potency opioids such as Pentazocine, Tramadol, Nalbuphine, and Tapentadol may also be considered with dose adjustments. Albeit less favorable, some other analgesic options include Gabapentin, Pregabalin, acetaminophen, Duloxetine, Venlafaxine, Fluoxetine, Topical Lidocaine, Capsaicin, and Clonidine. Methodology: A systematic literature search in PubMed and google scholar was conducted between March 5 and August 10, 2021. Articles were searched via search terms and keywords relating to International Classification of Diseases: hepatorenal syndrome, pain, opioids, metabolism, renal clearance. Results: One thousand three hundred eighty-seven articles were identified from database searching. After removal of duplicates, 924 studies were screened for eligibility. After review of titles and abstracts, 665 studies were rejected for relevance reasons. Most of these studies were rejected because they were not relevant, did not meet search criteria, case-control article, case series articles, no English translation, articles did not mention adjustments in patients with liver or kidney disease. One hundred forty-two articles were used for the synthesis.

Hypothyroidism Presenting as Reversible Renal Impairment

Certain studies have shown pathophysiology of diminished renal function in hypothyroidism. Aetiology is due to direct effect of thyroid hormone on kidney, and also the hemodynamic effects play an important role.

Case Report On Hepatorenal Syndrome

Hepatorenal syndrome (HRS) is a potentially reversible renal impairment where the kidney function is stopped due to renal vasoconstriction resulting from extreme vasodilation. This case report describes a 64 year old female with Decompensated Chronic Liver Disease. Her clinical history and physical findings shows a decreased renal function secondary to chronic liver disease and was later diagnosed as HRS. HRS can be managed effectively with Terlipressin, Midodrine, Albumin. Such combination therapy at the early stage of diagnosis can prevent further complications. Keywords: HRS, CLD, Albumin, Terlipressin, Midodrine.

The Addition of Carfilzomib to a Lenalidomide-Based Triplet Improves Outcomes in Newly Diagnosed Transplant Eligible Myeloma Patients with Renal Impairment: A Subgroup Analysis of the Myeloma XI Trial

The Addition of Carfilzomib to a Lenalidomide-Based Triplet Improves Outcomes in Newly Diagnosed Transplant Eligible Myeloma Patients with Renal Impairment: A Subgroup Analysis of the Myeloma XI Trial

Outcomes of early and reversible renal impairment in patients with ST segment elevation myocardial infarction undergoing percutaneous coronary intervention.

Acute kidney injury (AKI) is a frequent complication in patients with ST segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). While AKI occurring post-PCI has been well studied, the incidence and clinical significance of early renal impairment evident on hospital admission prior to PCI and which resolves towards discharge has not been investigated. We retrospectively studied 2339 STEMI patients treated with primary PCI. The incidence of renal impairment and in-hospital complications as well as short and long-term mortality were compared between patients who did not develop renal impairment, patients who developed post-PCI AKI and those who presented with renal impairment on admission but improved their renal function during hospitalization (improved renal function). Improved renal function was defined as continuous and gradual decrease of ⩾ 0.3 mg/dL in serum creatinine levels obtained at hospital admission. One hundred and nineteen patients (5%) had improved renal function and 230 patients (10%) developed post-PCI AKI. When compared with patients with no renal impairment, improved renal function and post-PCI AKI were associated with more complications and adverse events during hospitalization as well as higher 30-day mortality. Long-term mortality was significantly higher among those with post-PCI AKI (63/230, 27%) following STEMI than those without renal impairment (104/1990, 5%; p<0.001), but there was no significant difference in long term mortality between patients with no renal impairment and those with improved renal function (5% vs. 7.5%, p=0.17). In STEMI patients undergoing primary PCI, the presence of renal impairment prior to PCI which resolves towards discharge is not uncommon and is associated with adverse short-term outcomes but better long-term outcomes compared with post-PCI AKI.

Combined effect of pegylated interferon α with adefovir on renal function in Chinese patients with chronic hepatitis B.

Background:Long-term safety of treatment with hepatitis B virus (HBV) polymerase inhibitors is a concern. Adefovir dipivoxil (ADV) and/or interferon alfa (IFN-α) therapies have previously been associated with impairment of renal function. Limited data are available on the safety of combination therapy with nucleos (t)ide analogues (NAs) and IFN-α. The aim of this analysis was to assess the renal function during combined therapy with pegylated interferon α-2b (PEG-IFN-α-2b) and ADV versus PEG-IFN-α-2b alone in patients with chronic hepatitis B (CHB).Methods:We performed a multicenter, prospective, open-label, randomized-controlled trial of renal function data to investigate the efficacy of 48 weeks of therapy with PEG-IFN-α-2b and ADV versus PEG-IFN-α-2b alone in 102 patients with CHB in Anhui, China. Glomerular filtration rates (GFRs) were calculated by Cockcroft–Gault (CG), abbreviated Modification of Diet in Renal Disease (MDRD) study, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and were tested by repeated-measures 1-way analysis of variance within groups. A linear mixed effects model for repeated measures was also used to evaluate the association between baseline information and estimated glomerular filtration rate (eGFR) changes overtime in all enrolled patients. The model considered the baseline age, sex, HBV DNA, aminotransferase, treatment group, time, and group-by-time interaction as fixed effects and incorporated random effects for individual subjects.Results:After 48 weeks of therapy and further 24 weeks of follow-up, the eGFR decreased both in patients given PEG-IFN-α-2b single therapy and combined therapy. Age, HBV DNA, and combined therapy were significant negative predictive factors for eGFR changes.Conclusion:The incidence of renal adverse events in both groups was low, and the combination therapy may have delayed, but reversible renal impairment.

Diagnostik und Therapie des hepatorenalen Syndroms

Portal hypertension occurs frequently in advanced liver cirrhosis and accounts for the majority of lethal complications. Compensatory splanchnic vasodilation and counter regulatory mechanisms (e.g. activation of the renin-angiotensin-aldosterone system) increase renal vascular resistance, which may facilitate acute kidney injury and the development of hepatorenal syndrome (HRS). HRS represents a functional, yet reversible renal impairment with elevated serum creatinine levels. Establishing the diagnosis, fluid challenge test and several investigations are needed to exclude acute kidney injury and other causes of renal failure. Early treatment with albumin and vasoconstrictors improves the prognosis of HRS patients. The only curative treatment of HRS so far is improvement of liver function implying liver transplantation in many cases. TIPS placement may be useful as a bridging tool to transplantation unless hepatic encephalopathy is present. Spontaneous bacterial peritonitis (SBP) is a relevant, independent risk factor for HRS. In patients with liver cirrhosis and SBP in addition to antibiotics, preventive albumin treatment is recommended.

Relation of in-hospital serum creatinine change patterns and outcomes among ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.

The worsening of serum creatinine (sCr) level is a frequent finding among ST-segment elevation MI (STEMI) patients undergoing primary percutaneous coronary intervention (PCI), associated with adverse short-term and long-term outcomes. No information is present, however, regarding the incidence and prognostic implications associated with an improvement in sCr levels throughout hospitalization, as compared with admission levels. Reversible renal impairment prior to PCI is not associated with adverse outcomes. We retrospectively studied 1260 STEMI patients undergoing primary PCI. The incidence of in-hospital complications and long-term mortality was compared between patients having stable, worsened (>0.3 mg/dL increase), or improved (>0.3 mg/dL decrease) sCr levels throughout hospitalization. Overall, 127 patients (10%) had worsening in sCr levels, whereas 44 (3.5%) had an improvement of sCr compared with admission levels. Patients with worsening sCR had more complications during hospitalization, higher 30-day (13% vs 1%; P < 0.001) and up to 5-year all-cause mortality (28% vs 5%; P < 0.001) compared with those with stable sCR. No significant difference was found regarding complications and mortality between patients having an improvement in sCr and stable sCr. Compared with patients with stable sCr, the adjusted hazard ratio for all-cause mortality in patients with worsened sCr was 6.68 (95% confidence interval: 2.1-21.6, P = 0.002). In STEMI patients undergoing primary PCI, renal impairment prior to PCI is a frequent finding. In contrast to post-PCI sCr worsening, this entity is not associated with adverse short-term and long-term outcomes.

Hypothyroidism a reversible cause of renal dysfunction

Hypothyroidism is a systemic disorder characterized by low circulating thyroxine levels. Of late there was some western and sporadic literature from India on the association of hypothyroidism and reversible renal impairment. We here report this association from two of our patients, who presented to us with simultaneously elevated serum thyroid-stimulating hormone and creatinine levels.

Prolonged vitamin D intoxication: presentation, pathogenesis and progress

Vitamin D toxicity from unactivated vitamin D (calciferol) therapy is currently a rare cause of hypercalcaemia. However, the frequency of this event may increase as high-dose unactivated vitamin D preparations become available. Prolonged vitamin D toxicity can cause reversible hypercalcaemia and partially reversible renal impairment. Parathyroid hormone may not be suppressed with unactivated vitamin D toxicity, especially if renal disease coexists.

The Combination of Azacitidine (AZA) and Recombinant Erythropoietin (rEPO) Can Induce Rapidly Hematological Response In Intermediate-2 and High-risk MDS (including RAEB-t)

AbstractAbstract 2914 Background:AZA, a DNA hypomethylating agent, provides 50–60% responses in higher-risk MDS after administration of 6 courses of treatment. Recent laboratory data suggests that demethylation with AZA upregulates EPO-receptor mRNA (Wallach, 2009). AZA might also affect several genes involved in cell cycle, metabolism and signal transduction which are down-regulated in bone marrow erythroid cells in MDS patients non-responsive to rEPO. There is currently insufficient data to combine AZA and rEPO in MDS patients. Patients-Methods:We explored the safety and the efficacy of the AZA-rEPO combination in a cohort of 10 (M/F: 5/5) patients (pts) with a median age of 75(67-83) years. Diagnosis (WHO classification) was: RAEB-2: 5, CMML: 2 and RAEB-t: 3; IPSS was: int-2 in 8/10 and high in 2/10 pts. Median time from diagnosis was 6(1-31) months. 9/10 pts were transfusion dependent, 8/10 were refractory to previous rEPO administration while 2/10 pts were not treated with rEPO but their diagnostic serum EPO levels were >200 U/L. Patients were given AZA at FDA/EMEA-approved schedule (75 mg/m2/d x7d/4-weekly) initially for 5 courses and continued if response was obtained. rEPO (40,000IU/week) was given until achievement of steady Hb level >10.5 g/dL or until AZA discontinuation. Results:Median follow-up was 6.5(1-14) months. Patients received a median of 5 cycles (range 2–13) of AZA; 9/10 pts were treated with ≥5 courses of AZA. The median time of rEPO administration was 82(76-142) days. Best response (IWG 2006 criteria) was CR in 1/10 pts (RAEB-2: 1), marrow CR in 1/10 pts (RAEB-t: 1), and stable disease with hematological improvement (HI) in 4/10 pts (RAEB-t: 1, RAEB-2: 2, CMML: 1) leading to an overall response rate of 60%. As soon as 2 courses of AZA-rEPO were given, 5/6 responders experienced HI-erythroid response, 3/6 obtained HI-platelet response and 2/6 achieved HI-neutrophil response. Adverse events included 2 episodes of febrile neutropenia, nausea (2/10 pts), reversible renal impairment (2/10 pts) and hemorrhagic complications (3/10 patients). Currently, 9/10 patients remain alive, 1 patient experienced progression to AML and the estimated probability of 1 year-Progression Free Survival is 75%. Conclusions:This study provides clinical evidence that the AZA-rEPO combination is safe and rapidly effective in higher risk MDS pts. Our results emphasize the necessity for randomized trials in order to further evaluate the AZA-rEPO combination in MDS. Disclosures:No relevant conflicts of interest to declare.

Risk Score Predicting Decline in Renal Function Postliver Transplant: Role in Patient Selection for Combined Liver Kidney Transplantation

A combined liver and kidney transplantation (CLKT) is advocated for selected individuals with chronic kidney disease undergoing liver transplantation (LT). The aim was to develop a risk score to identify the patients whose estimated glomerular filtration rate (eGFR) would decline during the year post-LT to aid future patient selection for CLKT. A training dataset of LT recipients was identified retrospectively from a prospectively compiled database (2000-2007). The eGFR was calculated at 1 year and those with an eGFR less than 30 mL/min were identified. Variables determined at the LT assessment were analyzed by logistic regression, discriminant function, and area under the receiver operating characteristic curve (AUC) analysis to develop the score. The score was validated in a prospective patient cohort. Three hundred sixty-eight LT recipients were followed up for 1 year (training dataset). The mean eGFR declined by 11.2+/-23.5 mL/min during that time (P<0.001). A pre-LT risk score to predict an eGFR less than 30 mL/min at 1-year post-LT was generated: -1.8+(1.5 if a history of hypertension)+(0.65 x proteinuria in g/24 hr)+(0.013 x serum creatinine in micromol/L)+(0.001 x duration of acute kidney injury or eGFR <60 mL/min in days). Reversible renal impairment should first be excluded. Progression was likely with a score more than 2.16. Sensitivity, specificity, and AUC were 99.2%, 100%, and 0.99, respectively. All, but one patient, in the validation cohort (n=149) were correctly classified. This information will complement previously published criteria for CLKT patient selection.

Reversible renal impairment caused by thyroid disease

Renal impairment is a common finding in clinical practice and is increasingly recognized with the routine reporting of estimated glomerular filtration rates. Clinical assessment is essential to determine which of the many possible investigations are appropriate. Thyroid hormones regulate many cellular functions, and abnormalities of the active thyroid hormones, thyroxine (T(4)) and tri-iodothyronine (T(3)), can influence serum creatinine levels. Evaluation of thyroid function is easily overlooked, but important in this context, as hypothyroidism is common and can cause renal impairment, which is typically reversible. Renal dysfunction may also be more frequent in hyperthyroidism than is recognized. This report describe how a dramatic elevation in serum creatinine paralleled the development of hyperthyroidism, with a return of the creatinine to normal following treatment of the hyperthyroid state.

The Addition of Systemic High-Dose Methotrexate (HD-MTX) to Intrathecal Chemotherapy (IT) for Central Nervous System (CNS) Prophylaxis Substantilly Reduces CNS Recurrence Rates in Patients with at-Risk Aggressive Lymphoma: A Historically Controlled Prospective Study

CNS relapse is a devastating and usually fatal complication of NHL, and controversy exists regarding the best methods of CNS prophylaxis. We have previously shown that IT alone is inadequate in patients (pts) with aggressive NHL at high risk of CNS relapse (Leuk Lymphoma 2002; 43:1783). We therefore assessed the efficacy of adding systemic HD-MTX to IT prophylaxis, based on drug penetration into the CSF and brain parenchyma.Methods: from 1/91 to 3/08, 85 pts with newly diagnosed aggressive NHL and negative baseline CSF cytology were treated with CNS prophylaxis due to risk factors such as multiple extranodal (EN) sites and elevated LDH. Patients were classified into 3 groups:CHOP-like therapy & IT (n=24),systemic therapy incorporating HD-MTX (≥1g/m2 eg Hyper-CVAD; n=25) andCHOP-like therapy & IT followed by 2 doses of MTX 3g/m2 24 hour CIVI q14d (n=36).Results: Median age was 52 years (16–82). Groups 1, 2 and 3 were similar in proportions of advanced stage (III and IV), baseline LDH >1× ULN, gender, performance status and number of extranodal sites. Groups 2 & 3, who both received HD-MTX, were similar and were combined for all analyses. The CNS risk index (van Besien Blood 1998; 91;1178) was well matched for group 1 versus Groups 2/3 combined (P=0.3). The median number of IT treatments received was 5 (1 – 6) in group 1 and 6 (1 – 13) in groups 2/3. HD-MTX administration (total 101 admissions) was safe with a median 4(1–27) days inpatient stay and no treatment-related mortality. Complications included reversible renal impairment and mucositis grade ≥2 in 4% and 2% of cycles respectively. With a median follow-up of 29.5 months (2.6–164.4) there are 8 CNS relapses; 6 in group 1, 0 in group 2 and 2 in group 3. Sites of CNS recurrence were leptomeningeal alone in 4, isolated parenchymal in 2 and both in 2. All CNS recurrences occurred within 25.5 months (range 3.7–25.5) from diagnosis. Median survival after CNS relapse was 118 (14–264) days. Pts receiving systemic HD-MTX had a lower rate of CNS recurrence compared to group 1 pts (At 30 Mo; 4.5 ± 3% versus 27 ± 10%; P = 0.0033; figure 1). The only predictor for CNS relapse was the absence of systemic HD-MTX, with a hazard ratio of 10.07 (95%CI 2.16–46.97) for relapse in the IT-alone group (P=0.003). The relative risk of CNS relapse was 0.13 (0.03-0.6) in the groups treated with IT plus systemic HD-MTX. The 5-year actuarial CNS-relapse free survival rates were 42 ± 11% for group 1, and 82 ± 7% for groups 2/3 (P=0.0003).Conclusion: These data demonstrate that IT alone is inadequate CNS prophylaxis in at-risk patients with aggressive NHL. The addition of systemic HD-MTX either as part of primary therapy or administered following CHOP-like therapy significantly reduces CNS recurrence and may improve overall survival. [Display omitted]

Renal impairment resulting from hypothyroidism.

We describe two cases of reversible renal impairment secondary to hypothyroidism. We suggest that patients with renal impairment of unknown cause have thyroid function tests undertaken as part of routine investigation.

Renal impairment and hydronephrosis in a premature infant following morphine infusion: case report

This is a case report of an association between morphine administration and occurrence of hydronephrosis with acute renal failure. This premature female infant born at 27 weeks of gestation had moderate hydronephrosis with acute renal impairment while receiving morphine infusion for pain management after chest-tube insertion. All these findings were reversed after stopping morphine and urinary catheterization. Follow-up renal ultrasound and voiding cystourethrogram showed resolution of hydronephrosis with no evidence of vesicoureteral reflux. Morphine is associated with reversible hydronephrosis and renal impairment in premature infants.

Possible Interaction of Clozapine and Lisinopril

Back to table of contents Previous article Next article Letter to the EditorFull AccessPossible Interaction of Clozapine and LisinoprilGEORGE ABRAHAM, M.D., BEATRICE GRUNBERG, M.D., and SYLVIA GRATZ, M.D., GEORGE ABRAHAMSearch for more papers by this author, M.D., BEATRICE GRUNBERGSearch for more papers by this author, M.D., and SYLVIA GRATZSearch for more papers by this author, M.D., Philadelphia, Pa.Published Online:1 Jun 2001https://doi.org/10.1176/appi.ajp.158.6.969AboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Clozapine levels should be at 350–450 ng/ml for clinical efficacy and minimal side effects (1). Factors affecting its metabolism or excretion can influence clinical efficacy. We report on a patient who possibly experienced an interaction effect of clozapine and lisinopril.Mr. A, a 39-year-old Asian man with treatment-resistant schizophrenia, was receiving 300 mg/day of clozapine; his blood level of the drug was 490 ng/ml. In addition, he had diabetes that was controlled with glipizide, 10 mg/day. One year later, he developed hypertension, so lisinopril treatment, 5 mg/day, was initiated. Shortly afterward, his blood levels of clozapine and one its metabolites, norclozapine, were 966 ng/ml and 512 ng/ml, respectively. Six months later, his dose of lisinopril was increased to 10 mg/day. His blood levels of clozapine and norclozapine, as measured on two consecutive occasions 1 month apart, were 1092 and 380 ng/ml and 1245 and 392 ng/ml, respectively.Mr. A became more disorganized and had frequent episodes of irritability and angry outbursts. He experienced severe sleep disturbances and frequent nightmares and awakenings. He also salivated excessively. Other known side effects of clozapine, such as anticholinergic toxicity or seizures, were not observed. Laboratory values, including measures of renal functions, were found to be within normal limits.Mr. A’s clozapine dose was decreased to 200 mg/day. His blood levels, measured after 6 weeks, remained high: clozapine, 1335 ng/ml, and norclozapine, 428 ng/ml. When we suspected a drug interaction, his antihypertensive was changed from lisinopril to diltiazem, 240 mg/day. Repetition of laboratory tests after 6 weeks resulted in clozapine and norclozapine levels that had decreased to 693 and 254 ng/ml, respectively. Although Mr. A continued to experience psychotic symptoms and sialorrhea, his sleep disturbances and irritability had improved.An interaction in which lisinopril raises the level of clozapine or its metabolites has not been reported, to our knowledge. Angiotensin-converting enzyme inhibitors, by dilating efferent arterioles, decrease overall renal vascular resistance. This in turn decreases intraglomerular pressure, which reduces effective filtration pressure and slows the glomerular filtration rate, causing reversible renal impairment (2). This impairment may not be reflected by routine tests of renal function. Increased levels of norclozapine suggest impaired excretion.Lisinopril does not influence the cytochrome systems, and it is excreted unchanged in urine. Clozapine is metabolized by cytochrome 1A2 and 3A4 isoenzymes. It is a well-known phenomenon that excess levels of substrates cause abnormal enzymatic feedback control (3). In our patient, levels of both clozapine and norclozapine were elevated. It is not known whether accumulation of clozapine metabolites can cause negative feedback inhibition in the cytochrome P450 system. If so, it can cause an accumulation of the parent compound. The toxic effects of clozapine are known to cause sleep disturbances, with intensification of dream activity and immediate onset of REM sleep.

Reversible renal impairment induced by treatment with the angiotensin II receptor antagonist candesartan in a patient with bilateral renal artery stenosis

BackgroundIt is well established that ACE-inhibitors should be avoided in patients with renal artery stenosis. In recent years it has also been recommended that caution should be demonstrated when angiotensin II blockers are used in the same type of patients but the evidence is based only on few cases.ResultsWe describe a case where use of the angiotensin II antagonist candesartan (Atacand) induced renal failure in a patient with bilateral renal artery stenosis. The course of the case is enlighted by results from sequential renography, selective renal vein catheterisation for measurement of renin, and angiographic findings.ConclusionsIn patients with renal artery stenosis the angiotensin II antagonist candesartan should be avoided.

Successful preemptive cidofovir treatment for CMV antigenemia after dose-reduced conditioning and allogeneic blood stem cell transplantation.

Cidofovir (CDV) is a nucleotide analogue with proven in vitro effects against cytomegalovirus (CMV) and adenovirus and has been successfully used in the treatment of CMV retinitis in AIDS patients. We performed a prospective study to evaluate the efficacy of CDV in 17 patients with hematological malignancies after allogeneic blood stem cell transplantation from related (n=3) and unrelated (n=14) donors. Dose-reduced conditioning (DRC) regimen consisted of busulfan (Bu)/fludarabine (Flu) (n=9) and idarubicin/cytosine arabinoside/Flu (n=1). Myeloablative conditioning (MC) was performed with Bu/cyclophosphamide (Cy)/etoposide (Eto) (n=4), Bu/Cy (n=2), and total body irradiation (TBI)/Cy/Eto (n=1). Antithymocyte globulin (ATG) was used in seven patients with DRC and in six patients with MC. In all patients, either the donor, host, or both were CMV IgG positive pretransplant. Indication for therapy was preemptive treatment of primary CMV antigenemia defined as two consecutive positive tests of pp65 antigenemia assay after transplant. In case of response with a decreasing number of pp65-positive leukocytes, CDV was scheduled in a dosage of 5 mg/kg body weight once a week for 2 weeks followed by maintenance therapy every 2 weeks in an outpatient setting. All patients received probenecid and prehydration as recommended. Patients were monitored using an immunostaining assay for pp65 antigen and a qualitative and quantitative CMV polymerase chain reaction (PCR). Success of treatment was defined as negativity for the pp65 antigen. After DRC, nine of ten patients (90%) showed a response with seven of nine revealing a complete clearance of the virus (pp65 negative, qualitative PCR negative). In the remaining two responders, treatment was changed to ganciclovir because of either renal impairment or slow clearance of antigenemia. Only one of seven patients in the MC group experienced a temporary clearance of pp65 antigen. After MC, two patients experienced CMV disease. Treatment-related toxicity rate was moderate with four patients developing reversible renal impairment (creatinine 133-180 micromol/L); one patient with proteinuria and three patients with complaints of nausea and vomiting. Our data suggest the feasibility of CDV administration in patients after allogeneic transplantation. In the recommended dose, it might be used successfully for low-risk patients, e.g., after DRC or organ transplantation, in an outpatient setting.

Ifosfamide, cisplatin and etoposide combination in locally advanced inoperable non-small-cell lung cancer: a phase II study

From March 1993 to February 1997, 43 eligible patients with inoperable stage IIIA (ten patients) and stage IIIB (33 patients), histologically confirmed NSCLC received 3 courses of the ICE combination (ifosfamide 1.5 g m−2 and mesna 750 mg m−2 two times a day, cisplatin 25 mg m−2 and etoposide 100 mg m−2, all administered intravenously (i.v.) on days 1–3 every 3 weeks) with G-CSF support. After three cycles, patients were submitted to radical surgery or received two additional courses of the ICE regimen and/or curative radiotherapy. Grade 3–4 neutropenia occurred in 21% of 114 evaluable courses, but was of short duration, leading to neutropenic fever in 5% of the courses. Severe thrombocytopenia and anaemia were observed in 13% and 3% of the courses respectively. Non-haematological toxicity was generally mild with only two episodes of reversible renal impairment. The overall response rate after three chemotherapy courses was 69% (28 partial responses, one complete response). Ten patients (8/10 patients in stage IIIA, 2/33 patients in stage IIIB) underwent radical surgery. Median TTP for patients not undergoing surgery (n = 33) was 8 months (range 3–34+); median DFS for patients rendered NED by surgery (n = 10) was 26 months (range 1–54+). Median OS for the entire group was 12.5 months (range 2–57+). The ICE regimen is active in locally advanced NSCLC with acceptable toxicity and warrants further exploration as induction chemotherapy in larger series. © 1999 Cancer Research Campaign