Timothy Price | The University of Adelaide (original) (raw)

Papers by Timothy Price

Gastrointestinal Oncology, 2002

Background: Carboplatin is frequently substituted for cisplatin in chemotherapy protocols due to ... more Background: Carboplatin is frequently substituted for cisplatin in chemotherapy protocols due to greater tolerability. However in certain tumour groups, including oesophageal carcinoma, carboplatin is considered to be less active. ... Objective: The purpose of this study was to ...

Oncology (Williston Park, N.Y.)

ABSTRACT

Clinical colorectal cancer, Jan 30, 2015

Colorectal cancer (CRC) is a common malignancy. There is growing evidence that CRC incidence is i... more Colorectal cancer (CRC) is a common malignancy. There is growing evidence that CRC incidence is increasing in the younger population. There is controversy surrounding the prognosis of young patients with CRC. In this study we reviewed Australian patients with metastatic CRC (mCRC) who were younger than 40 years of age at the time of diagnosis of metastatic disease. To our knowledge this is the first study to focus on this age group with mCRC. This was a retrospective study using data from the South Australian Metastatic Colorectal Cancer database. We compared patient and disease characteristics, management approaches, and outcomes for age groups < 40 and ≥ 40. A multivariate Cox proportional hazards model was fitted to compare the survival outcomes (death from all causes) between the 2 groups. From 3318 patients, 46 (1.4%) were younger than 40 years of age. In a comparison of patients in the younger than 40-year-old group with the older group, a greater proportion had synchronous...

Objective: This study evaluated the long term outcomes to neoadjuvant paclitaxel and epirubicin (... more Objective: This study evaluated the long term outcomes to neoadjuvant paclitaxel and epirubicin (PE) followed by post-operative cyclophosphamide, methotrexate and fluorouracil (CMF) in women with Stage III breast cancer.

Expert opinion on drug metabolism & toxicology, 2015

Integration of targeted therapy and additional chemotherapy options has improved median overall s... more Integration of targeted therapy and additional chemotherapy options has improved median overall survival (OS) in patients with unresectable metastatic colorectal cancer (mCRC). Cetuximab and panitumumab are examples of targeted therapies, specifically against the epidermal growth factor receptor (EGFR). This review focuses on Panitumumab, a fully human IgG2 monoclonal antibody, which inhibits key oncogenic downstream cell signalling pathways. Panitumumab and cetuximab have improved tumour response rate, progression-free survival, and OS in mCRC patients in whom the RAS (Rat Sarcoma) gene is of Wild Type (WT) status. The EGFR signalling pathway and preclinical, Phase I and Phase II clinical studies on the pharmacokinetic, pharmacodynamic and safety evaluation of panitumumab are presented. Phase III studies utilising panitumumab in the first, second and third line setting in mCRC are also described. Panitumumab exhibits excellent pharmacokinetics and pharmacodynamics by way of uncompl...

$Research paper thumbnail of A phase 1/2 study of Lyprinol in advanced hormone refractory prostate cancer, and hormone and chemotherapy refractory breast cancer$

The Australian journal of rural health, Jan 10, 2015

This study aims to investigate disparities in demographics, disease characteristics, treatment an... more This study aims to investigate disparities in demographics, disease characteristics, treatment and overall survival between South Australian (SA) Indigenous and non-Indigenous patients with metastatic colorectal cancer (mCRC). This employs a retrospective population study using the SA mCRC registry. The SA mCRC registry identifies mCRC patients from hospital encounters, histopathology reports, medical oncology letters, clinician notification, attendances at multidisciplinary meetings and death audits by the SA Cancer Registry. A total of 2865 adult mCRC patients including 14 Indigenous patients were identified through the SA mCRC registry between February 2006 and August 2013. Patients were linked to the SA Cancer Registry to obtain Indigenous status. Demographic, disease and treatment characteristics were compared using Chi-squared test and t-test; while overall survival defined as time to any cause of death was analysed using Cox regression. No difference was observed for clinical...

Molecular diagnosis & therapy, Jan 29, 2015

Patients with metastatic colorectal cancer (mCRC) with BRAF mutation (BRAF MT) generally have a p... more Patients with metastatic colorectal cancer (mCRC) with BRAF mutation (BRAF MT) generally have a poorer prognosis. BRAF MT may also have implications for treatment strategy. Despite this, inclusion of BRAF in routine molecular testing varies. Here we report the frequency of BRAF reporting in the South Australian (SA) mCRC registry reflecting community practice, together with the survival outcomes based on mutation status. The SA population-based mCRC registry was analysed to assess the number of patients where a BRAF MT result was available. The patient characteristics are reported and overall survival was analysed using the Kaplan-Meier method. Of the 3639 patients who have been entered in the registry, only 6.2 % (227) have BRAF MT results available. Of the patients tested, the BRAF MT rate is 12.7 %. The mutation rate was highest in rightsided primary; right colon 23 versus left colon 8.9 % and rectum 7 %. There was no significant difference in median age or male/female proportion...

Clinical Lymphoma Myeloma and Leukemia, 2015

World journal of gastroenterology, Jan 7, 2015

Colorectal cancer (CRC) is a common malignancy worldwide. In CRC patients, metastases are the mai... more Colorectal cancer (CRC) is a common malignancy worldwide. In CRC patients, metastases are the main cause of cancer-related mortality. In a group of metastatic CRC patients, the metastases are limited to a single site (solitary organ); the liver and lungs are the most commonly involved sites. When metastatic disease is limited to the liver and/or lungs, the resectability of the metastatic lesions will dictate the management approach and the outcome. Less commonly, the site of solitary organ CRC metastasis is the peritoneum. In these patients, cytoreduction followed by hyperthermic intraperitoneal chemotherapy may improve the outcome. Rarely, CRC involves other organs, such as the brain, bone, adrenals and spleen, as the only site of metastatic disease. There are limited data to guide clinical practice in these cases. Here, we have reviewed the disease characteristics, management approaches and prognosis based on the metastatic disease site in patients with CRC with metastases to a si...

Asian Pacific journal of cancer prevention : APJCP, 2011

Kidney cancer has a high incidence in Australia by world standards but has attracted little publi... more Kidney cancer has a high incidence in Australia by world standards but has attracted little public health attention because of its low ranking among other cancers as a cause of death. Incidence, mortality and survival trends were investigated in this study for an Australian population and cancer control opportunities considered. Age-standardized incidence and mortality rates were analyzed by broad age category using data from an Australian cancer registry. Disease-specific survivals were analyzed using the Kaplan-Meier product limit estimate and multivariable Cox proportional hazards regression. Incidence rates approximately doubled during 1980-2008, with large increases affecting both sexes. Increases were more evident for renal cell and other histology types occurring predominantly in adulthood than childhood nephroblastomas. The male to female incidence ratio approximated 2:1 but decreased over time and was lower in younger than older age groups. The increase in mortality rate wa...

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 31, 2015

To report the final efficacy findings and biomarker analysis from the NO16968 trial comparing bol... more To report the final efficacy findings and biomarker analysis from the NO16968 trial comparing bolus fluorouracil/folinic acid (FU/FA) with capecitabine plus oxaliplatin (XELOX) in resected stage III colon cancer. After curative resection, patients were randomly assigned to receive XELOX, as oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1,000 mg/m(2) twice daily on days 1 to 14 every 3 weeks, or bolus FU/FA, as the Mayo Clinic or Roswell Park regimens, for 6 months. The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS). The intention-to-treat population comprised 1,886 patients (XELOX, n = 944; FU/FA, n = 942). Seven-year DFS rates were 63% and 56% in the XELOX and FU/FA groups, respectively (hazard ratio [HR], 0.80; 95% CI, 0.69 to 0.93; P = .004). Seven-year OS rates were 73% and 67% in the XELOX and FU/FA groups, respectively (HR, 0.83; 95% CI, 0.70 to 0.99; P = .04). A total of 68% and 77% of patients who experienced relaps...

Clinical Cancer Research, 2015

We evaluated the influence of RAS mutation status on the treatment effect of panitumumab in a pro... more We evaluated the influence of RAS mutation status on the treatment effect of panitumumab in a prospective-retrospective analysis of a randomized, multicenter phase 3 study of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) versus FOLFIRI alone as second-line therapy in patients with metastatic colorectal cancer (mCRC; ClinicalTrials.gov, NCT0039183). Outcomes were from the study&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s primary analysis. RAS mutations beyond KRAS exon 2 (KRAS exons 3, 4; NRAS exons 2, 3, 4; BRAF exon 15) were detected by bidirectional Sanger sequencing in wild-type KRAS exon 2 tumor specimens. Progression-free survival (PFS) and overall survival (OS) were coprimary endpoints. The RAS ascertainment rate was 85%; 18% of wild-type KRAS exon 2 tumors harbored other RAS mutations. For PFS and OS, the hazard ratio for panitumumab plus FOLFIRI versus FOLFIRI alone more strongly favored panitumumab in the wild-type RAS population than in the wild-type KRAS exon 2 population (PFS HR, 0.70 [95%CI=0.54‒0.91];P=0.007 versus 0.73 [95%CI=0.59-0.90];P=0.004; OS HR, 0.81 [95%CI=0.63‒1.03];P=0.08 versus 0.85 [95%CI=0.70‒1.04];P=0.12). Patients with RAS mutations were unlikely to benefit from panitumumab. Among RAS wild-type patients, the objective response rate was 41% in the panitumumab-FOLFIRI group versus 10% in the FOLFIRI group. Patients with RAS mutations were unlikely to benefit from panitumumab-FOLFIRI and the benefit-risk of panitumumab-FOLFIRI was improved in the wild-type RAS population compared to the wild-type KRAS exon 2 population. These findings support RAS testing for patients with mCRC.

Cancer medicine, Jan 25, 2015

Although a raised body mass index (BMI) is associated with increased risk of colorectal cancer (C... more Although a raised body mass index (BMI) is associated with increased risk of colorectal cancer (CRC) and recurrence after adjuvant treatment, data in the metastatic setting is limited. We compared overall survival (OS) across BMI groups for metastatic CRC, and specifically examined the effect of BMI within the group of patients treated with targeted therapies (TT). Retrospective data were obtained from the South Australian Registry for mCRC from February 2006 to October 2012. The BMI at first treatment was grouped as underweight <18.5 kg/m(2) , Normal = 18.5 to <25 kg/m(2) , Overweight = 25 to <30 kg/m(2) , Obese I = 30 to <35 kg/m(2) , Obese II ≥35 kg/m(2) . Of 1174 patients, 42 were underweight, 462 overweight, 175 Obese I, and 77 Obese II. The OS was shorter for patients who were underweight and overweight compared to normal (OS 13.7 and 22.3 vs. 24.1 months, respectively, hazard ratio [HR] 2.21 and 1.23). The adjusted median OS was longer for normal versus overweight...

PLOS ONE, 2015

The EGFR inhibitors (EGFR-I) cetuximab and panitumumab and the angiogenesis inhibitors (AIs) beva... more The EGFR inhibitors (EGFR-I) cetuximab and panitumumab and the angiogenesis inhibitors (AIs) bevacizumab and aflibercept have demonstrated varying efficacy in mCRC.