Biomedical subjects

D Stark

Publications and source records attributed to D Stark.

At least 19 recordsLinked to original sources

PubMed2007

PCR detection of Entamoeba histolytica, Entamoeba dispar, and Entamoeba moshkovskii in stool samples from Sydney, Australia.

This study investigated the presence of Entamoeba histolytica, Entamoeba dispar, and Entamoeba moshkovskii in stool samples from a patient population in Sydney, Australia. Stool samples were tested by microscopy and PCR. Five patients were found with E. histolytica infections, while E. dispar and E. moshkovskii were observed in 63 (70.8%) and 55 (61.8%) patients, respectively, by PCR. This is the first study in Australia using molecular techniques to determine the presence of E. histolytica, E. dispar, and E. moshkovskii.

Adult↗

PubMed2007

The initial development of an item bank to assess and screen for psychological distress in cancer patients.

Psychological distress is a common problem among cancer patients. Despite the large number of instruments that have been developed to assess distress, their utility remains disappointing. This study aimed to use Rasch models to develop an item-bank which would provide the basis for better means of assessing psychological distress in cancer patients.An item bank was developed from eight psychological distress questionnaires using Rasch analysis to link common items. Items from the questionnaires were added iteratively with common items as anchor points and misfitting items (infit mean square >1.3) removed, and unidimensionality assessed.A total of 4914 patients completed the questionnaires providing an initial pool of 83 items. Twenty items were removed resulting in a final pool of 63 items. Good fit was demonstrated and no additional factor structure was evident from the residuals. However, there was little overlap between item locations and person measures, since items mainly targeted higher levels of distress. The Rasch analysis allowed items to be pooled and generated a unidimensional instrument for measuring psychological distress in cancer patients. Additional items are required to more accurately assess patients across the whole continuum of psychological distress.

Adolescent↗

PubMed2006

Veillonella parvula discitis and secondary bacteremia: a rare infection complicating endoscopy and colonoscopy?

We report a case of Veillonella parvula lumbar discitis and secondary bacteremia confirmed by molecular characterization of the 16S rRNA genes. Identification of the organism was essential for an appropriate choice of antimicrobial therapy following the failure of empirical flucloxacillin. Veillonella spp. are normal flora of the gastrointestinal tract, raising the possibility that an endoscopy and colonoscopy performed 8 weeks prior to presentation, during which small intestinal and rectal biopsies were obtained, was the portal of entry. This case highlights the importance of obtaining a microbiologic diagnosis, particularly in patients who previously have had procedures involving instrumentation.

Bacteremia↗

PubMed2006

Conservative management of pelvic organ prolapse in women.

BACKGROUND: Pelvic organ prolapse is common, and some degree of prolapse is seen in 50% of parous women. Women with prolapse can experience a variety of pelvic floor symptoms. Treatments include surgery, mechanical devices and conservative management. Conservative management approaches, such as giving lifestyle advice and delivering pelvic floor muscle training, are often used in cases of mild to moderate prolapse. OBJECTIVES: To determine the effects of conservative management (physical interventions and lifestyle interventions) for women with pelvic organ prolapse in comparison with no treatment or other treatment options (such as mechanical devices or surgery). SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Trials Register (searched on 19 September 2005), MEDLINE (January 1966 to August 2005), MEDLINE In Process & Other Citations (15 September 2005), EMBASE (January 1996 to Week 43 2005), CINAHL (January 1982 to October 2005), PEDro (September 2005), the UK National Research Register (Issue 3, 2005), the US National Institute of Health clinical trial register (5 October 2005), Current Controlled Trials register (5 October 2005), Controlled Clinical Trials (September 2005) and ZETOC (September 2005). We searched the reference lists of relevant articles. SELECTION CRITERIA: Randomised and quasi-randomised trials in women with pelvic organ prolapse that included a physical or lifestyle intervention in at least one arm of the trial. DATA COLLECTION AND ANALYSIS: Two reviewers assessed all trials for inclusion/exclusion and methodological quality. Data were extracted by the lead reviewer onto a standard form and cross checked by another. Disagreements were resolved by discussion. Data were processed as described in the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: Three trials of relevance to this review were identified. The largest of these, of pelvic floor muscle training in preventing anterior prolapse from worsening, had significant limitations which affect the generalisability and rigor of the findings. A small feasibility study (which is to be followed up with a larger trial) randomised 47 women to pelvic floor muscle training or control and found suggestions of better outcomes (better self-reported improvement, decreased severity) in the intervention group. The third trial evaluated peri-operative physiotherapy for women undergoing surgery for prolapse and/or incontinence. The authors report that urinary symptoms, pelvic floor muscle function and quality of life were improved more in the treatment group than the control group, but data were not provided to allow this to be assessed. The trial was small and no prolapse-specific outcome measures were used. It was not possible to combine data from the three trials. AUTHORS' CONCLUSIONS: Despite there now being reports of three eligible trials in this update, the evidence available is not significant to guide practice. There is some encouragement from a feasibility study that pelvic floor muscle training, delivered by a physiotherapist to symptomatic women in an outpatient setting, may reduce severity of prolapse. Further evidence from larger, better quality randomised control trials is however still necessary.

Adult↗

PubMed2006

Irritable bowel syndrome: a review on the role of intestinal protozoa and the importance of their detection and diagnosis.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder in which abdominal pain is associated with a defect or a change in bowel habits. Gut inflammation is one of the proposed mechanisms of pathogenesis. Recent studies have described a possible role for protozoan parasites, such as Blastocystis hominis and Dientamoeba fragilis, in the etiology of IBS. Dientamoeba fragilis is known to cause IBS-like symptoms and has a propensity to cause chronic infections but its diagnosis relies on microscopy of stained smears, which many laboratories do not perform, thereby leading to the misdiagnosis of dientamoebiasis as IBS. The role of B. hominis as an etiological agent of IBS is inconclusive, due to contradictory reports and the controversial nature of B. hominis as a human pathogen. Although Entamoeba histolytica infections occur predominately in developing regions of the world, clinical diagnosis of amebiasis is often difficult because symptoms of patients with IBS may closely mimic those patients with non-dysenteric amoebic colitis. Clinical manifestations of Giardia intestinalis infection also vary from asymptomatic carriage to acute and chronic diarrhoea with abdominal pain. These IBS-like symptoms can be continuous, intermittent, sporadic or recurrent, sometimes lasting years without correct diagnosis. It is essential that all patients with IBS undergo routine parasitological investigations in order to rule out the presence of protozoan parasites as the causative agents of the clinical signs.

Animals↗

PubMed2006

Evaluation of three diagnostic methods, including real-time PCR, for detection of Dientamoeba fragilis in stool specimens.

Dientamoeba fragilis is a protozoan parasite of humans that infects the mucosa of the large intestine and is associated with gastrointestinal disease. We developed a 5' nuclease (TaqMan)-based real-time PCR assay, targeting the small subunit rRNA gene, for the detection of D. fragilis in human stool specimens and compared its sensitivity and specificity to conventional PCR and microscopic examination by a traditional modified iron-hematoxylin staining procedure. Real-time PCR exhibited 100% sensitivity and specificity.

Animals↗

PubMed2006

Post-kala-azar dermal leishmaniasis due to Leishmania infantum in a human immunodeficiency virus type 1-infected patient.

We report the first case of post-kala-azar dermal leishmaniasis due to Leishmania infantum in a human immunodeficiency virus type 1-infected patient in Australia. Molecular characterization of the isolate was performed using PCR restriction fragment length polymorphism targeting both repetitive sequences from Leishmania nuclear DNA and repetitive kinetoplast DNA minicircles for species differentiation.

AIDS-Related Opportunistic Infections↗

PubMed2006

Topotecan, pegylated liposomal doxorubicin hydrochloride and paclitaxel for second-line or subsequent treatment of advanced ovarian cancer: a systematic review and economic evaluation.

OBJECTIVES: To examine the clinical effectiveness and cost-effectiveness of intravenous formulations of topotecan monotherapy, pegylated liposomal doxorubicin hydorocholoride (PLDH) monotherapy and paclitaxel used alone or in combination with a platinum-based compound for the second-line or subsequent treatment of advanced ovarian cancer. DATA SOURCES: Electronic databases covering publication years 2000-4. Company submissions. REVIEW METHODS: Seventeen databases were searched for randomised controlled trials (RCTs) and systematic reviews for the clinical effectiveness of PLDH, topotecan and paclitaxel and economic evaluations of the cost-effectiveness of PLDH, topotecan and paclitaxel. Selected studies were quality assessed and data extracted, as were the three company submissions. A new model was developed to assess the costs of the alternative treatments, the differential mean survival duration and the impact of health-related quality of life. Monte-Carlo simulation was used to reflect uncertainty in the cost-effectiveness results. RESULTS: Nine RCTs were identified. In five of these trials, both the comparators were used within their licensed indications. Of these five, three included participants with both platinum-resistant and platinum-sensitive advanced ovarian cancer, and a further two only included participants with platinum-sensitive disease. The comparators that were assessed in the three trials that included both subtypes of participants were PLDH versus topotecan, topotecan versus paclitaxel and PLDH versus paclitaxel. In the further two trials that included participants with the subtype of platinum-sensitive disease, the comparators that were assessed were single-agent paclitaxel versus a combination of cyclophosphamide, doxorubicin and cisplatin (CAP) and paclitaxel plus platinum-based chemotherapy versus conventional platinum-based therapy alone. A further four trials were identified and included in the review in which one of the comparators in the trial was used outside its licensed indication. The comparators assessed in these trials were oxaliplatin versus paclitaxel, paclitaxel given weekly versus every 3 weeks, paclitaxel at two different dose levels and oral versus intravenous topotecan. Four studies met the inclusion criteria for the cost-effectiveness review. The review of the economic evidence from the literature and industry submissions identified a number of significant limitations in existing studies assessing the cost-effectiveness of PLDH, topotecan and paclitaxel. Analysis 1 assessed the cost-effectiveness of PLDH, topotecan and paclitaxel administered as monotherapies. Sensitivity analysis was undertaken to explore the impact of patient heterogeneity (e.g. platinum-sensitive and platinum-resistant/refractory patients), the inclusion of additional trial data and alternative assumptions regarding treatment and monitoring costs. In the base-case results for Analysis 1, paclitaxel monotherapy emerged as the cheapest treatment. When the incremental cost-effectiveness ratios (ICERs) were estimated, topotecan was dominated by PLDH. Hence the options considered in the estimation of the ICERs were paclitaxel and PLDH. The ICER for PLDH compared with paclitaxel was pound 7033 per quality-adjusted life-year (QALY) in the overall patient population (comprising platinum-sensitive, -refractory and -resistant patients). The ICER was more favourable in the platinum-sensitive group ( pound 5777 per QALY) and less favourable in the platinum-refractory/resistant group ( pound 9555 per QALY). The cost-effectiveness results for the base-case analysis were sensitive to the inclusion of additional trial data. Incorporating the results of the additional trial data resulted in less favourable estimates for the ICER for PLDH versus paclitaxel compared with the base-case results. The ICER of PLDH compared with paclitaxel was pound 20,620 per QALY in the overall patient population, pound 16,183 per QALY in the platinum-sensitive population and pound 26,867 per QALY in the platinum-resistant and -refractory population. The results from Analysis 2 explored the cost-effectiveness of the full range of treatment comparators for platinum-sensitive patients. The treatment options considered in this model comprised PLDH, topotecan, paclitaxel-monotherapy, CAP, paclitaxel/platinum combination therapy and platinum monotherapy. Owing to the less robust approaches that were employed to synthesise the available evidence and the heterogeneity between the different trials, the reliability of these results should be interpreted with some caution. Topotecan, paclitaxel monotherapy and PLDH were all dominated by platinum monotherapy (i.e. higher costs and lower QALYs). After excluding these alternatives, the treatments that remained under consideration were platinum monotherapy, CAP and paclitaxel-platinum combination therapy. Of these three alternatives, platinum monotherapy was the least costly and least effective. The ICER for CAP compared with platinum monotherapy was pound 16,421 per QALY. The ICER for paclitaxel-platinum combination therapy compared with CAP was pound 20,950 per QALY. CONCLUSIONS: For participants with platinum-resistant disease there was a low probability of response to treatment with PLDH, topotecan or paclitaxel. Furthermore, there was little difference between the three comparators in relation to overall survival. The comparators did, however, differ considerably in their toxicity profiles. Given the low survival times and response rates, it appears that the maintenance of quality of life and the control of symptoms and toxicity are paramount in this patient group. As the three comparators differed significantly in terms of their toxicity profiles, patient and physician choice is also an important element that should be addressed when decisions are made regarding second-line therapy. It can also be suggested that this group of patients may benefit from being included in further clinical trials of new drugs. For participants with platinum-sensitive disease there was a considerable range of median survival times observed across the trials. The most favourable survival times and response rates were observed for paclitaxel and platinum combination therapy. This suggests that treatment with combination therapy may be more beneficial than treatment with a single-agent chemotherapeutic regimen. In terms of single-agent compounds, the evidence suggests that PLDH is more effective than topotecan. Evidence from a further trial that compared PLDH and paclitaxel suggests that there is no significant difference between these two comparators in this trial. The three comparators did, however, differ significantly in terms of their toxicity profiles across the trials. Although treatment with PLDH may therefore be more beneficial than that with topotecan, patient and physician choice as to the potential toxicities associated with each of the comparators and the patient's ability and willingness to tolerate these are of importance. Assuming the NHS is willing to pay up to pound 20,000-40,000 per additional QALY, PLDH appears to be cost-effective compared with topotecan and paclitaxel monotherapy, in terms of the overall patient population and the main subgroups considered. The cost-effectiveness results for the base-case analysis were sensitive to the inclusion of additional trial data. Incorporating the results of additional trial data gave less favourable estimates for the ICER for PLDH versus paclitaxel monotherapy, compared with the base-case results. Although the ICER of PLDH compared with paclitaxel monotherapy was less favourable, PLDH was still cost-effective compared with topotecan and paclitaxel monotherapy. For platinum-sensitive patients, the combination of paclitaxel and platinum appears to be cost-effective. On the strength of the evidence reviewed here, it can be suggested that participants with platinum-resistant disease may benefit from being included in further clinical trials of new drugs. To assess the effectiveness of combination therapy against a single-agent non-platinum-based compound, it can be suggested that a trial that compared paclitaxel in combination with a platinum-based therapy versus single-agent PLDH would be a reasonable option.

Antibiotics, Antineoplastic↗

PubMed2005

Detection of Dientamoeba fragilis in fresh stool specimens using PCR.

Dientamoeba fragilis is a trichomonad parasite that causes human gastrointestinal disease. Currently microscopy is considered to be the gold standard for diagnosis of D. fragilis infection. However, this method is time-consuming and relatively insensitive. A PCR assay based on the small-subunit ribosomal RNA gene of D. fragilis for the specific detection of D. fragilis DNA in fresh unpreserved stool samples was developed. The D. fragilis PCR was positive in 29/31 samples with positive microscopy and did not cross-react with other protozoan parasites. The PCR protocol showed a specificity of 100% and a sensitivity of 93.5% and the entire procedure can be performed in one day.

Animals↗

PubMed2005

Prospective study of the prevalence, genotyping, and clinical relevance of Dientamoeba fragilis infections in an Australian population.

A prospective study was conducted over a 30-month period, in which fecal specimens from 6,750 patients were submitted to the Department of Microbiology at St. Vincent's Hospital, Sydney, Australia. Trophozoites of Dientamoeba fragilis were detected in 60 (0.9%) patients by permanent staining, and confirmation was performed by PCR. Gastrointestinal symptoms were present in all patients, with diarrhea and abdominal pain the most common symptoms. Thirty-two percent of patients presented with chronic symptoms. The average age of infected patients was 39.8 years. No correlation was found between D. fragilis and Enterobius vermicularis, a proposed vector of transmission for D. fragilis. The genetic diversity of 50 D. fragilis isolates was examined by PCR, and the PCR products were analyzed for the presence of restriction fragment length polymorphisms. These results showed no variation in the small-subunit rRNA gene and demonstrated a single genotype for all Australian isolates. This study shows the potential pathogenic properties of D. fragilis and the need for all laboratories to routinely test for this organism.

Abdominal Pain↗

PubMed2004

Reassurance and the anxious cancer patient.

Many cancer patients are anxious even when disease is in remission. Anxiety about health, 'health anxiety', has distinct features, notably seeking medical reassurance about symptoms. Doctors may then communicate that these symptoms are not due to serious illness, a process known as 'reassurance'. However, reassurance may inadvertently perpetuate some patients' anxiety. We aimed to observe the relation between symptoms, anxiety and reassurance in consultations with cancer patients. A total of 95 outpatients, with breast or testicular cancers in remission, completed questionnaires measuring health anxiety at study entry, then general anxiety - before a consultation, immediately afterwards, 1 week later, and before their next consultation. We examined symptoms reported and reassurance by oncologists from audio recordings of consultations, and the outcome of subjects' anxiety. The results showed that substantial health anxiety was reported by one-third of the patients. Patients with higher levels of health anxiety reported more symptoms during consultations. Reassurance was ubiquitous, but not followed by an enduring improvement in anxiety. Certain forms of reassurance predicted increased anxiety over time, particularly for subjects who were most anxious. In conclusion, health anxiety can be a problem after cancer. Reassurance may not reduce patients' anxiety. Some reassurance was counterproductive for the most anxious patients. Oncologists may need to use reassurance as a procedure, balancing risk, and benefits, and patient selection and to manage cancer patients in remission.

Adolescent↗

PubMed2004

Conservative management of pelvic organ prolapse in women.

Adult↗

PubMed2004

An integrated approach to management of Marfan syndrome caused by an FBN1 exon 18 mutation in an Australian Aboriginal family.

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Adolescent↗

PubMed2003

Novel type of in situ extraction: Use of solvent containing microcapsules for the bioconversion of 2-phenylethanol from L-phenylalanine by Saccharomyces cerevisiae.

A novel in situ product removal (ISPR) method that uses microcapsules to extract inhibitory products from the reaction suspension is introduced into fermentation technology. More specifically, L-phenylalanine (L-Phe) was transformed by Saccharomyces cerevisiae to 2-phenylethanol (PEA), which is inhibitory toward the yeast. In order to continuously remove PEA from the vicinity of the cells, the reaction suspension was brought into contact with capsules of 2.2-mm diameter that had a hydrophobic core of dibutyl sebacate and an alginate-based wall. This novel process combines the advantages of a normal in situ extraction process (fast mass transfer and simple process set-up) with the benefits of a membrane-based process (reduction of the solvent toxicity and avoidance of stable emulsions). In particular, the microbial cells are shielded from the phase toxicity of the organic solvent by a hydrogel layer surrounding the organic core. By placing the microcapsules into the fermenter, the final overall concentration of PEA in a fed-batch culture was increased from 3.8 to 5.6 g/L because a part of the inhibitory product dissolved in the dibutyl sebacate core. In another fermentation experiment, the capsules were placed in a fluidized bed that was connected via a loop to the fermenter. In addition, the fluidized bed was connected via a second loop to a back-extractor to regenerate the capsules. By alternating the extraction and back-extraction cycles, it was possible to limit the PEA concentration of the fed-batch culture in the fermenter to 2.4 g/L while producing important quantities of PEA that accumulated in an external reservoir.

Adsorption↗

PubMed2002

Anxiety disorders in cancer patients: their nature, associations, and relation to quality of life.

PURPOSE: We aimed to estimate the prevalence and types of anxiety disorders diagnosed according to standardized criteria in cancer patients, to compare screening tools in detecting them, and to examine their demographic, oncologic, and psychosocial associations. METHODS: In this cross-sectional observational study of 178 subjects with lymphoma, renal cell carcinoma, malignant melanoma, or plasma cell dyscrasia, we related responses to questionnaires (administered by computer touch-screen) measuring psychological symptoms, quality of life (QOL), and social support to standardized psychiatric interviews and cancer management. RESULTS: Forty-eight percent of subjects reported sufficient anxiety for anxiety disorder to be considered. At subsequent diagnostic interview, 18% fulfilled International Classification of Disorders, 10th Revision criteria for anxiety disorder, including 6% of patients who reported low levels of anxiety by questionnaire. When subjects reported anxiety by questionnaire, if disruptive somatic anxiety was present, this increased the probability of diagnosable anxiety disorder from.31 to.7. The most accurate screening questionnaires were the trait scale of the State-Trait Anxiety Inventory and the Hospital Anxiety and Depression scale. Female sex and negative aspects of social support were associated with anxiety disorder in multivariate analyses. Anxiety disorder was independently associated with a deficit in QOL, particularly insomnia. CONCLUSION: Anxiety symptoms are common in cancer patients. Screening by questionnaire seems to assess anxiety symptoms adequately but discriminates abnormal anxiety inadequately. To improve this, we may need to use criteria such as disruption from anxiety, as illustrated by the impact of anxiety disorders on QOL. There seem to be few oncologic variables that could target screening for anxiety disorders.

Adult↗

PubMed2001

Mutations in the sterol-sensing domain of Patched suggest a role for vesicular trafficking in Smoothened regulation.

The tumor suppressor gene patched (ptc) encodes an approximately 140 kDa polytopic transmembrane protein [1-3] [corrected] that binds members of the Hedgehog (Hh) family of signaling proteins [4-6] [corrected] and regulates the activity of Smoothened (Smo), a G protein-coupled receptor-like protein essential for Hh signal transduction [7-9] [corrected]. Ptc contains a sterol-sensing domain (SSD) [10, 11] [corrected], a motif found in proteins implicated in the intracellular trafficking of cholesterol [12] [corrected], and/or other cargoes [13-15] [corrected]. Cholesterol plays a critical role in Hedgehog (Hh) signaling by facilitating the regulated secretion and sequestration of the Hh protein [16] [corrected], to which it is covalently coupled. In addition, cholesterol synthesis inhibitors block the ability of cells to respond to Hh [18, 19] [corrected], and this finding points to an additional requirement for the lipid in regulating downstream components of the Hh signaling pathway. Although the SSD of Ptc has been linked to both the sequestration of, and the cellular response to Hh [16, 20, 21] [corrected], definitive evidence for its function has so far been lacking. Here we describe the identification and characterization of two missense mutations in the SSD of Drosophila Ptc; strikingly, while both mutations abolish Smo repression, neither affects the ability of Ptc to interact with Hh. We speculate that Ptc may control Smo activity by regulating an intracellular trafficking process dependent upon the integrity of the SSD.

Amino Acid Sequence↗

PubMed2001

Self-reported quality of life of individual cancer patients: concordance of results with disease course and medical records.

PURPOSE: To investigate the applicability of a standard quality of life (QL) questionnaire to individual cancer patients and to explore the potential for impact of QL information on the process of care by comparing at group level the QL results with the medical records. PATIENTS AND METHODS: One hundred fourteen consecutive patients at the oncology clinics at St James's Hospital, Leeds, United Kingdom, completed the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 on a touch-screen computer over a 6-month period. The QL results were compared with the corresponding medical records at individual and group level. RESULTS: For individual patients, the serial measurement of QL allowed recognition of patterns over time corresponding to disease course. At group level, a higher proportion of patients reported problems on EORTC QLQ-C30 than were mentioned in the medical records (McNemar paired test, P <.01). Most often clinicians mentioned pain (22% to 39%), and at the initial visit role (66%), and social issues (77%). For the rest of the symptoms and functions, the problems were recorded in between 1% and 25% of the notes, but 20% to 76% of the patients reported QL impairment. Problems that were not recorded in the medical notes tended to be of low severity, with a significant trend observed for pain, fatigue, nausea/vomiting, dyspnea, loss of appetite, and physical function scale (chi(2) test, 11.55 to 34.42, df = 1, P <.001). CONCLUSION: The QL data on individual patients was consistent with the clinical records, thus providing evidence for the validity of these measures in assessment of the individual. The QL profiles had more information on symptoms and particularly on functional issues, such as emotional distress and physical performance.

Disease Progression↗

PubMed2000

Received dose and dose-intensity of chemotherapy and outcome in nonmetastatic extremity osteosarcoma. European Osteosarcoma Intergroup.

PURPOSE: To examine the relationship between received dose, received dose-intensity (RDI), and survival in patients with osteosarcoma. PATIENTS AND METHODS: Between 1983 and 1993, the European Osteosarcoma Intergroup (EOI) conducted two randomized trials involving patients with high-grade, nonmetastatic, biopsy-proven osteosarcoma of the extremity. These trials shared a common treatment arm of doxorubicin (DOX) 75 mg/m(2) and cisplatin (CDDP) 100 mg/m(2) planned for six cycles at 3-week intervals. Definitive surgery was scheduled at week 9, after three cycles. Survival time was calculated from 122 days, the scheduled end of chemotherapy. RESULTS: A total of 287 patients randomized to DOX/CDDP received at least one cycle of chemotherapy, and 232 (81%) received all six cycles. On average, 79% of the intended dose of DOX and 80% of the intended dose of CDDP was given. Mean time to completion of chemotherapy was 1.27 times that specified by the protocol. Mean RDI was 0.64 for DOX (SD = 0.19) and 0.65 for CDDP (SD = 0.18). Progression-free survival was lower for those who received one to five cycles compared with those who completed all six cycles (hazards ratio, 1.69; 95% confidence interval, 1.03 to 2.78). Survival and progression-free survival were lowest for patients with RDI less than 0.6, although these differences were not statistically significant at the 5% level. There was no clear evidence of preoperative dose or dose-intensity influencing histologic response. CONCLUSION: This analysis did not establish a clear survival benefit for increasing received dose or dose-intensity in the context of this two-drug regimen. The hypothesis that increasing dose-intensity may improve survival in osteosarcoma requires prospective evaluation.

Adolescent↗