The value of local registry data for describing cervical cancer management and outcomes over three decades in Australia.

Registry data on invasive cervical cancers (n = 1,274) from four major hospitals (1984-2012) were analysed to determine their value for informing local service delivery in Australia. The methodology comprised disease-specific survival analyses using Kaplan-Meier product-limit estimates and Cox proportional hazards models and treatment analyses using logistic regression. Five- and 10-year survivals were 72% and 68%, respectively, equating with relative survival estimates for Australia and the USA. Most common treatments were surgery and radiotherapy. Systemic therapies increased in recent years, generally with radiotherapy, but were less common for residents from less accessible areas. Surgery was more common for younger women and early-stage disease, and radiotherapy for older women and regional and more advanced disease. The proportion of glandular cancers increased in-step with national trends. Little evidence of variation in risk-adjusted survival presented over time or by Local Health District. The study illustrates the value of local registry data for describing local treatment and outcomes. They show the lower use of systemic therapies among residents of less accessible areas which warrants further investigation. Risk-adjusted treatment and outcomes did not vary by socio-economic status, suggesting equity in service delivery. These data are important for local evaluation and were not available from other sources.

A Mosaic Expression of a Hb J-Amiens (HBB: c.54G > T; p.Lys18Asn) and its Interference with Hb A1c Analysis.

We report the case of a 56-year-old Caucasian woman in whom hemoglobinopathy screening was triggered following an aberrant Hb A1c analysis. Preliminary diagnosis of the hemoglobin (Hb) variant was obtained through cation exchange high performance liquid chromatography (HPLC) and gel electrophoresis. DNA analysis confirmed the presence of Hb J-Amiens [ß17(A14)Lys→Asn; HBB: c.[54G > C or 54G > T)]. However, an unbalanced ratio between wild type and mutant signal after direct sequencing and a lower than expected percentage of this Hb variant led to the suggestion of a mosaic expression. Furthermore, different methods [capillary zone electrophoresis (CZE), cation exchange HPLC and boronate affinity] were tested to study the possible interference of this variant with Hb A1c measurements. These investigations showed a clinically relevant difference between the methods tested. Hb A1c analysis may lead to the discovery of new Hb variants or mosaicism for previously described Hb variants. This may have genetic consequences for the offspring of carriers and brings about the question of partner testing.

Dutch national guidelines for locally recurrent rectal cancer.

Due to improvements in treatment for primary rectal cancer, the incidence of LRRC has decreased. However, 6-12% of patients will still develop a local recurrence. Treatment of patients with LRRC can be challenging, because of complex and heterogeneous disease presentation and scarce - often low-grade - data steering clinical decisions. Previous consensus guidelines have provided some direction regarding diagnosis and treatment, but no comprehensive guidelines encompassing all aspects of the clinical management of patients with LRRC are available to date. The treatment of LRRC requires a multidisciplinary approach and overarching expertise in all domains. This broad expertise is often limited to specific expert centres, with dedicated multidisciplinary teams treating LRRC. A comprehensive, narrative literature review was performed and used to develop the Dutch National Guideline for management of LRRC, in an attempt to guide decision making for clinicians, regarding the complete clinical pathway from diagnosis to surgery.

Implementation of an Enhanced Recovery after Surgery Protocol in Advanced and Recurrent Rectal Cancer Patients after beyond Total Mesorectal Excision Surgery: A Feasibility Study.

INTRODUCTION: The implementation of an Enhanced Recovery After Surgery (ERAS) protocol in patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) has been deemed unfeasible until now because of the heterogeneity of this disease and low caseloads. Since evidence and experience with ERAS principles in colorectal cancer care are increasing, a modified ERAS protocol for this specific group has been developed. The aim of this study is to evaluate the implementation of a tailored ERAS protocol for patients with LARC or LRRC, requiring beyond total mesorectal excision (bTME) surgery. METHODS: Patients who underwent a bTME for LARC or LRRC between October 2021 and December 2022 were prospectively studied. All patients were treated in accordance with the ERAS LARRC protocol, which consisted of 39 ERAS care elements specifically developed for patients with LARC and LRRC. One of the most important adaptations of this protocol was the anaesthesia procedure, which involved the use of total intravenous anaesthesia with intravenous (iv) lidocaine, iv methadone, and iv ketamine instead of epidural anaesthesia. The outcomes showed compliance with ERAS care elements, complications, length of stay, and functional recovery. A follow-up was performed at 30 and 90 days post-surgery. RESULTS: Seventy-two patients were selected, all of whom underwent bTME for either LARC (54.2%) or LRRC (45.8%). Total compliance with the adjusted ERAS protocol was 73.6%. Major complications were present in 12 patients (16.7%), and the median length of hospital stay was 9 days (IQR 6.0-14.0). Patients who received multimodal anaesthesia (75.0%) stayed in the hospital for a median of 7.0 days (IQR 6.8-15.5). These patients received fewer opioids on the first three postoperative days than patients who received epidural analgesia (p < 0.001). CONCLUSIONS: The implementation of the ERAS LARRC protocol seemed successful according to its compliance rate of >70%. Its complication rate was substantially reduced in comparison with the literature. Multimodal anaesthesia is feasible in beyond TME surgery with promising effects on recovery after surgery.

[Anxiety and mood disorders are independent risk factors for cardiovascular diseases]. / Stemmings- en angststoornissen als risicofactor voor cardiovasculaire ziekten.

OBJECTIVE: Psychiatric conditions are insufficiently highlighted as cardiovascular risk factors in the CVRM guideline. Objectives of this review are 1) to determine if anxiety and mood symptoms/disorders are independent cardiovascular risk factors; 2) to compare this risk to a population without these psychiatric conditions and 3) to ascertain the influence of psychiatric disease severity. DESIGN: Narrative systematic review METHOD: We searched for meta-analyses and systematic reviews in PubMed. Quality assessment by AMSTAR criteria. RESULTS: 10 reviews were included from 172 hits. (Sub)clinical depression and mood disorders are associated with an increased independent risk to develop cardiovascular diseases, coronary artery disease, myocardial infarction and cerebrovascular disease. Bipolar disorders increase the cerebrovascular risk, but not myocardial infarction. Anxiety disorders/symptoms heighten the cardiovascular, myocardial and cerebrovascular risk. CONCLUSION: Anxiety and mood symptoms/disorders are independent cardiovascular risk factors. Severe anxiety and mood disorders should be included as separate risk factors in the CVRM guideline.

Serous carcinoma of the uterus-determination of HER-2/neu status using immunohistochemistry, chromogenic in situ hybridization, and quantitative polymerase chain reaction techniques: its significance and clinical correlation.

Uterine serous papillary carcinoma (USPC) are high-grade tumors with Her2 gene expression and poor prognosis. The human gene Her2 is a proto-oncogene that encodes a protein with tyrosine kinase activity. The objective of this study was to determine Her2 protein expression and gene amplification in USPC using three methods: immunohistochemistry (IHC), chromogenic in situ hybridization (CISH), and quantitative polymerase chain reaction (Q-PCR), to compare the three techniques, and to correlate Her2 expression and amplification with clinical outcome. Clinical data were obtained from the records of the patients provided by the database of the Gynaecological Cancer Unit at the Royal Adelaide Hospital. Paraffin-embedded tissues of 45 cases were examined using three techniques. Her2 positive rate was 40%. About 13% was strongly positive by all three methods. About 67% Her2 positive patients had advanced-stage disease. Relapse rate was 61% (P = 0.6). Stages I and II had a better survival with negative receptor. Age and stage were major prognostic variables in Cox analysis. Marker status did not reach statistical significance in overall survival (OS) and relapse-free survival (RFS), but had a hazard ratio (HR) of 1.5 in RFS. Five-year OS with Her2 negative was 39%. HR was 0.97 (95% CI 0.46-2.1). RFS was 39% and HR was 1.4 (95% CI 0.65-2.9). The three methods have strong correlation. IHC, 3+ positive cases should be regarded as exhibiting evidence of gene amplification and do not require further testing. Equivocal results require further testing by CISH or PCR. Age and stage are strong prognostic variables and receptor status has a HR of 1.5 in RFS. The therapeutic role of Trastuzumab should be tested in clinical trial setting.

Antenatal corticosteroids for women at risk of imminent preterm birth in low-resource countries: the case for equipoise and the need for efficacy trials.

The scientific basis for antenatal corticosteroids (ACS) for women at risk of preterm birth has rapidly changed in recent years. Two landmark trials-the Antenatal Corticosteroid Trial and the Antenatal Late Preterm Steroids Trial-have challenged the long-held assumptions on the comparative health benefits and harms regarding the use of ACS for preterm birth across all levels of care and contexts, including resource-limited settings. Researchers, clinicians, programme managers, policymakers and donors working in low-income and middle-income countries now face challenging questions of whether, where and how ACS can be used to optimise outcomes for both women and preterm newborns. In this article, we briefly present an appraisal of the current evidence around ACS, how these findings informed WHO's current recommendations on ACS use, and the knowledge gaps that have emerged in the light of new trial evidence. Critical considerations in the generalisability of the available evidence demonstrate that a true state of clinical equipoise exists for this treatment option in low-resource settings. An expert group convened by WHO concluded that there is a clear need for more efficacy trials of ACS in these settings to inform clinical practice.

Evaluation of (99m)Tc-labeled tropanes with alkyl substituents on the 3beta-phenyl ring as potential dopamine transporter tracers.

Technetium(V)-oxo-3beta-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-yl[N-(2-mercaptoethyl), N-(N'-(2-mercaptoethyl)-2-aminoethyl)]-aminomethyl ((99m)Tc-TRODAT-1) and three derivatives with one or two substituents on the 3beta-phenyl ring (4-methylphenyl, 4-ethylphenyl and 2,4-dimethylphenyl) were prepared and evaluated as potential imaging agents for the central nervous dopamine transporter (DAT). Labeling of the ligands with (99m)Tc yielded for each of them a mixture of two radiolabeled species, which were purified and isolated using reversed-phase high-performance liquid chromatography. Employing radio-LC-MS, we found both species to have the same molecular mass suggesting diastereoisomers. After intravenous injection in mice and rats, the compounds were stable in vivo and no important metabolites were found in plasma or urine. Replacement of the 4-chloro atom on the 3beta-phenyl ring by a methyl group causes no loss of affinity for the DAT system. However, substitution of an ethyl group for the 4-chloro atom or introduction of a second methyl group in the 2-position of the phenyl ring results in a serious reduction of the affinity for the DAT transporter. Ex vivo autoradiography on mice brain slices and biodistribution studies in rats showed specific uptake of (99m)Tc-TRODAT-1 and the 4-methylphenyl derivative in striatum and putamen. Although the 4-ethylphenyl and 2,4-dimethylphenyl derivatives show brain uptake in rats and mice, no specific uptake in striatum was found. In addition, differences in biological behavior between the different diastereomers were observed. In conclusion, small changes to (99m)Tc-TRODAT-1 at the phenyl ring in the 3beta position of the tropane moiety significantly change the biological behavior of the studied compounds.

Biological evaluation of a technetium-99m-labeled integrated tropane-BAT and its piperidine congener as potential dopamine transporter imaging agents.

INTRODUCTION: Recently, we have reported modification of (99m)Tc-TRODAT-1 by integrating the N2S2 metal chelating unit and the tropane skeleton. Results of a preliminary biodistribution study in rats were promising with respect to brain uptake. The present report deals with the further biological characterization of the (99m)Tc-labelled integrated TRODAT derivatives ((99m)Tc-TropaBAT and (99m)Tc-norchloro-TropaBAT) and with the synthesis and biological evaluation of a novel (99m)Tc-labelled piperidine-based derivative ((99m)Tc-PipBAT). METHODS: Biodistribution of all radiolabelled complexes was studied in normal mice. A more detailed ex vivo intracerebral distribution study of the two (99m)Tc-TropaBAT complexes was additionally performed in normal rats. Autoradiography of brain sections of normal mice (with or without pretreatment with FP-beta-CIT or haloperidol) and rats was performed. Affinity for the dopamine transporter (DAT) was also assessed in vitro in the presence or absence of cocaine. RESULTS: Both (99m)Tc-TropaBAT complexes show a slightly higher brain uptake than (99m)Tc-TRODAT-1, but the striatum/cerebellum activity ratio is less favourable. Nevertheless, significant striatal uptake was detected after ex vivo autoradiography, but this uptake was also observed after pretreatment with FP-beta-CIT. Unexpectedly, no striatal uptake was detected after in vitro incubation of mouse brain sections with the tracer agents. For (99m)Tc-PipBAT, neither brain uptake nor in vitro striatal uptake was found. CONCLUSION: Both (99m)Tc-TropaBAT complexes exhibit similar diffusion into brain as (99m)Tc-TRODAT-1, and ex vivo autoradiography shows significant striatal uptake. However, the inferior striatum/cerebellum activity ratio, the striatal uptake in mice pretreated with FP-beta-CIT or haloperidol, and the lack of striatal uptake during in vitro incubation prove that the DAT is not targeted. Brain uptake disappears when the tropane skeleton is replaced by a piperidine ring, and also in this case no striatal uptake is found in vitro.

Evaluation of the V8 E-Class, a Novel Automated Capillary Isoelectric Focusing Instrument for Hemoglobinopathy Screening.

OBJECTIVES: We evaluated the performance of a novel capillary isoelectric focusing (CIEF) application for hemoglobinopathy screening on the recently introduced V8 E-Class platform. METHODS: Analytical performance of the V8 E-Class was evaluated and included assessment of hemoglobin A2 (HbA2) imprecision; linearity for HbA2, fetal hemoglobin (HbF), and sickle hemoglobin (HbS); and carryover for HbS. Furthermore, a method comparison with the Minicap Flex Piercing (Sebia, Lisses, France), the Variant Classic (Bio-Rad Laboratories, Hercules, CA), and the G8 (Tosoh Europe, Amsterdam, the Netherlands) was done to assess analytical and clinical concordance. RESULTS: Total HbA2 imprecision was 3.26% and 3.14% for normal and elevated HbA2 controls and 5.16% and 3.58% for a normal and a heterozygous HbS patient sample, respectively. HbA2, HbF, and HbS showed acceptable linearity, and no carryover was observed. The method comparison showed good analytical concordance (r > 0.95) except for a homozygous HbS subset (r = 0.532-0.704). A comparable phenomenon was seen for the clinical concordance with good agreement in samples without variants (weighted κ > 0.80) but poorer agreement in HbS samples (κ < 0.30). CONCLUSIONS: Good analytical performance was demonstrated for this novel CIEF application for hemoglobinopathy screening. Method comparison showed generally good correlation but highlights the need for standardization. Finally, software optimization could further add to its use for routine hemoglobinopathy screening.

Disposition of unchanged cisplatin in patients with ovarian cancer.

The disposition of cisplatin (cis-diamminedichloroplatinum II) was studied in the first course of treatment in seven patients (56 +/- 12 years) with ovarian carcinoma by analytic methodology specific for the unchanged drug. Particular attention was paid to rapid blood and urine sample processing to avoid drug losses. Patients were catheterized for urine collections. During and after infusion, plasma levels of unbound cisplatin were simultaneously fitted to a one-compartment model. Creatinine clearance was determined at the same time as cisplatin renal clearance and was 38 +/- 16 ml/min/m2. Total clearance of unbound cisplatin was 253 +/- 48 ml/min/m2 and volume of distribution was 11.5 +/- 2.7 L/m2. Cisplatin half-life was similar when determined from plasma (31.6 +/- 6.0 minutes) or urinary excretion rate data (24.4 +/- 4.0 minutes). Urinary excretion of unchanged drug was 23.3% +/- 8.6% of the dose and renal clearance 56.9 +/- 18.0 ml/min/m2. Renal clearance exceeded creatinine clearance in all patients ratio = 1.9 +/- 1.2), confirming previous suggestions of active renal tubular secretion of cisplatin. Renal clearance was nonlinear with time in two of the patients who received the 2-hour infusion, possibly reflecting changing renal tubular reabsorption. Pharmacokinetic studies of unchanged cisplatin rather than total platinum are therefore practical and could be pursued in further studies defining cisplatin disposition in patients.

Misonidazole combined with radiotherapy in the treatment of carcinoma of the uterine cervix.

Between April 1979 and January 1982, 331 patients were included in a study to establish whether misonidazole (MISO) had any effect as an adjuvant to radiotherapy in the treatment of squamous cell carcinoma of the uterine cervix (FIGO Stage IIb, III, and IVa). Patients were randomized to receive either MISO (12 g/m2 applied within 6 weeks) or placebo. This was given in conjunction with each institution's normal radiotherapy schedule and thus varied with regard to external and intracavitary irradiation. The analysis was performed based on patients' status at January 1986, with all patients observed for at least 4 years. One hundred and sixty-four patients received MISO and 167 placebo. Compliance to radiotherapy was good and MISO was well tolerated. The overall rates for MISO vs. placebo were as follows: local tumour control, 50 vs. 54%; disease-free survival, 47 vs. 46%, and crude survival, 39 vs. 45%. A similar lack of MISO effect was found in the individual stages. However, patients in all stages with hemoglobin concentrations below 7 mmol/l had a significantly lower local control probability (overall 24 vs. 47%), whereas the incidence of distant metastases was unaffected. We conclude that the addition of MISO did not influence the radiation response in advanced uterine carcinoma. The reasons for this ineffectiveness are yet to be clarified.

Presynaptic beta-adrenoceptors in rat atria: evidence for the presence of stereoselective beta 1-adrenoceptors.

1. Presynaptic beta-adrenoceptor activity was studied in rat isolated atria, previously loaded with [3H]-noradrenaline. The stimulation-induced release of 3H transmitter was measured in the presence of cocaine, and adrenaline was used as a facilitatory beta-adrenoceptor agonist. 2. Adrenaline (0.1 and 2 nM) increased, by about 50%, the evoked efflux of tritium. With phenoxybenzamine present, the same activity was shown with 10 nM adrenaline. 3. The beta 2-selective adrenoceptor blocking drugs: IPS 339 and ICI 118 551 caused a concentration-dependent decrease in the activity of adrenaline. Cardioselective beta-blocking drugs: acebutolol, beta-xolol, nebivolol and its isomers (R 67 138 and R 67 145) also reduced dose-dependently the agonistic action of adrenaline. The order of potency for nebivolol and its isomers was R 67 138 greater than nebivolol greater than R 67 145. The activity of pindolol was not concentration-dependent. The inhibitory effect of acebutolol was also observed in the presence of blockade of alpha-adrenoceptors. 4. The postsynaptic beta-adrenoceptor blocking activity of nebivolol and its isomers was studied in pithed rats. They reduced isoprenaline-induced tachycardia without altering hypotensive responses. The order of potency was: R 67 138 greater than nebivolol greater than R 67 145. 5. It is concluded that in rat isolated atria, presynaptic beta 2- and beta 1-adrenoceptors coexist and that facilitatory beta 1-adrenoceptors are stereospecific.

Biochemical characterization of the mechanisms involved in the 5-hydroxytryptamine-induced increase in rat atrial rate.

Several possible mechanisms for 5-hydroxytryptamine (5-HT)-induced tachycardia in rat have been suggested: an activation of 5-HT1C or 5-HT2 receptors, an indirect sympathomimetic effect or a mechanism independent of 5-HT2 receptor stimulation. The aim of this study was to investigate the involvement of these mechanisms in the 5-HT-induced increase in rat atrial rate using biochemical methods. Indeed, the 5-HT1C and 5-HT2 receptors are linked to phosphoinositide hydrolysis and the noradrenaline (NA) released by 5-HT can stimulate the beta 1-adrenergic receptors linked to adenylate cyclase stimulation. The effect of varying concentrations of 5-HT on inositol phospholipid hydrolysis and adenylate cyclase activity of the rat isolated atria were measured. 5-HT (2 microM) did not modify total inositol phosphate (IP) production, while 5-HT 10 and 50 microM increased it 2-fold. The 5-HT2 antagonist ketanserin (1 microM) abolished IP accumulation induced by 5-HT microM), which indicates that this accumulation is 5-HT2 and not 5-HT1C receptor-mediated. Moreover, cyclic AMP (cAMP) formation was enhanced by 5-HT (5, 10, 20 and 50 microM). When atria were incubated 10 min with the beta-adrenergic receptor antagonist nadolol (1 microM), the increase in the cAMP level induced by 5-HT, whatever its concentration (10, 20 or 50 microM), was inhibited. Treating rats with reserpine (2.5 mg/kg, i.p., 48 and 24 hr before experimentation), which caused NA depletion in the heart, seemed to reduce the stimulating effect of 5-HT 10 and 50 microM on adenylate cyclase activity. Thus, the 5-HT-induced increase in cAMP is indirectly due to the activation of the beta-adrenergic receptors by the NA released by 5-HT. It is concluded that 5-HT stimulates both phosphoinositide turnover and adenylate cyclase activity in the rat isolated atria by activation of 5-HT2 receptors and by an indirect sympathomimetic effect.

Comparison of haematological recovery times and supportive care requirements of autologous recovery phase peripheral blood stem cell transplants, autologous bone marrow transplants and allogeneic bone marrow transplants.

The haematological recovery time, infection rate and supportive care requirements of patients receiving recovery phase autologous peripheral blood stem cell transplants (APBSCT) (n = 38), autologous bone marrow transplants (autoBMT) (n = 13) and allogeneic bone marrow transplants (alloBMT) (n = 14) were compared with respect to the time post-transplant to reach 0.1, 0.5 and 2.0 x 10(9) neutrophils/l and 50 and 150 x 10(9) platelets/l, the length of hospitalization, fever and antibiotic use, the incidence of documented infection and the number of red cell and platelet transfusions. The APBSCT group had a significantly more rapid recovery of neutrophils and platelets and their supportive care requirements were significantly less than the autoBMT and the alloBMT groups. There was no difference between the latter two groups. The most significant variables contributing to the differences in haematological recovery times were the granulocyte-macrophage progenitor (CFU-GM) dose infused and, to a lesser extent, patient age. The APBSCT group received a higher CFU-GM dose of 87 +/- 12 x 10(4)/kg BW compared with 12 +/- 5 and 17 +/- 3 x 10(4)/kg BW in the autoBMT and the alloBMT groups, respectively (p = 0.0001). Patient age showed a negative correlation with the rate of recovery because the APBSCT group, which recovered faster was also older (48 +/- 2 years, compared with 33 +/- 3 and 31 +/- 2, respectively, p = 0.0001). On multivariate analysis, CFU-GM dose was the only variable to show a significant correlation with all the haematological recovery endpoints studied in these 65 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic factors in patients with stage I epithelial ovarian cancer.

We analyzed factors predictive of relapse risk in patients with stage I invasive epithelial ovarian cancer: 252 patients from the Princess Margaret Hospital provided a data base for hypothesis generation, and data on 267 patients from the Norwegian Radium Hospital were used for hypothesis testing. The outcomes in most analyses in the two series were very similar, validating the following conclusions. Differentiation (grade) was the most powerful predictor of relapse, followed by dense adherence (which resulted in outcomes equivalent to those in stage II) and, finally, large-volume ascites. When the effects of these three factors were accounted for, then none of the following were prognostic: bilaterality (stage Ib), cyst rupture (stage Ic), capsular penetration (stage Ic), tumor size, histologic subtype, patient age, year of diagnosis, and postoperative therapy. These results allow simplification of stage I substaging, as only differentiation, dense adherence, and large-volume ascites (? peritoneal cytology) need be considered. The 5-year relapse-free rate was 98% in patients with grade 1 tumors in whom both dense adherence and large-volume ascites were absent. These patients are adequately treated by operation alone. Although the relapse risk was high enough in the remaining patients to warrant postoperative treatment, a significant benefit could be shown only for a small subset of patients, namely those with densely adherent tumors treated with abdominopelvic radiotherapy. In grades 2 and 3, none of the therapies used in either series was superior to pelvic radiotherapy or operation alone.

A pharmacokinetic evaluation of IM administration of bleomycin oil suspension.

Bleomycin oil suspension was given IM twice daily to four patients, and bleomycin saline solution infused to three patients with cervical carcinoma. The serum levels of bleomycin were followed for 12 h by radioimmunoassay. Both regimens revealed comparable side effects. Only minor responses were seen. Bleomycin oil suspension produced prolonged levels of bleomycin in serum.

Influence of infusion time on unchanged cisplatin disposition in patients with ovarian cancer.

The disposition of unchanged cisplatin in ten patients with ovarian cancer receiving 2-h infusions of 100 mg/m2 was compared with that of ten patients receiving 6-h infusions. A high-performance liquid chromatographic assay specific for the unchanged drug was used and all collected samples were rapidly processed. Patients were catheterized for urine collections. Cisplatin renal clearance was significantly lower after 6-hour infusions (52.8 +/- 16.2 ml/min per m2) than after 2-h infusions (87.1 +/- 38.2 ml/min per m2) (P = 0.026). Total clearance was also lower and less variable, although not significantly, in patients receiving the longer infusion. No differences in nonrenal clearance, volume of distribution, or half-life were observed between the two groups. There was only a poor relationship between cisplatin renal clearance and creatinine clearance after 2-h (r2 = 0.02; P = 0.66) and 6-h infusions (r2 = 0.18; P = 0.23). A single cisplatin plasma level obtained at the end of the infusion proved to be a good predictor of total cisplatin clearance after both 2-h (r2 = 0.70; P = 0.0096) and 6-h infusions (r2 = 0.97; P = 0.0001). This level was not significantly related to the relatively small changes in creatinine clearance that occurred after three courses of treatment.