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P J Ross

Publications and source records attributed to P J Ross.

At least 19 recordsLinked to original sources
PubMed2001

Antisense treatment directed against mutated Ki-ras in human colorectal adenocarcinoma.

BACKGROUND: Kirsten ras (Ki-ras) mutations are common in gastrointestinal cancer and one codon 12 mutation, glycine to valine, is particularly aggressive in colorectal cancer. AIMS: To investigate if this valine point mutation could be targeted with antisense oligonucleotides and to determine the efficacy of any antisense/mRNA interaction. METHODS: Twenty nine antisense oligonucleotides were screened against target and control Ki-ras RNA in a cell free system and against target and control cell lines in culture. RESULTS: The activity and specificity of the oligonucleotides varied. Results for the individual oligonucleotides were consistent in a cell free model and in cell culture using two different uptake promoters. Only one oligonucleotide was specific in its cleavage of target Ki-ras mRNA in the cell free system and appeared specific in cell culture, although changes in Ki-ras mRNA and protein expression following a single treatment could not be detected. Experiments in the cell free system showed that the point mutation is relatively inaccessible to oligonucleotides. Other sites on the Ki-ras RNA molecule, away from the point mutation, can be targeted more effectively. CONCLUSIONS: Successful targeting of the clinically relevant Ki-ras point mutation with antisense oligonucleotides is difficult because of RNA structure at the mutated site and is inefficient compared with other sites on the Ki-ras mRNA.

Adenocarcinoma↗
PubMed2000

ECF in gastric cancer.

Explore the source record for details and available documents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Phase I study of irinotecan and raltitrexed in patients with advanced gastrointestinal tract adenocarcinoma.

To determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of irinotecan and raltitrexed given as sequential short infusions every 3 weeks, 33 patients with pretreated gastrointestinal adenocarcinoma (31 colorectal, 2 oesophagogastric) entered this open label dose-escalation study. For the first five dose levels patients received irinotecan 175-350 mg m(-2) followed by raltitrexed 2.6 mg m(-2). Level VI was irinotecan 350 mg m(-2) plus raltitrexed 3.0 mg m(-2), level VII was irinotecan 400 mg m(-2) plus raltitrexed 2.6 mg m(-2); 261 courses were administered. Only one patient at dose levels I-V experienced DLT. At level VI, 5/12 patients experienced DLT: one had grade 3 diarrhoea and lethargy, one had grade 4 diarrhoea and one had lethargy alone. Two others had lethargy caused by disease progression. There was no first-cycle neutropenia. At level VII, 3/6 patients experienced dose-limiting lethargy, one also had grade 3 diarrhoea. Dose intensity fell from over 90% for both drugs at level VI to 83% for irinotecan and 66% for raltitrexed at level VII. Lethargy was therefore the DLT, and level VII the MTD. Pharmacokinetic data showed no measurable drug interaction; 6/30 patients (20%) had objective responses. This combination is active with manageable toxicity. Recommended doses for further evaluation are irinotecan 350 mg m(-2) and raltitrexed 3.0 mg m(-2).

Adenocarcinoma↗
PubMed1999

Influence of metastatic site as an additional predictor for response and outcome in advanced colorectal carcinoma.

Every year, 31,230 men and women are diagnosed with colorectal carcinoma, and up to 60% of these will ultimately develop advanced disease. However, there is little information to identify which patients are most likely to benefit from palliative chemotherapy. This analysis is unique in evaluating how the site of metastasis influences response and survival. A database of 497 patients treated within randomized clinical trials using 5-Fluorouracil (5FU)-based chemotherapy at the Royal Marsden Hospital was analysed. The potential for site of metastasis as a predictive variable for response to chemotherapy and survival was examined, in addition to other clinical parameters. The presence of liver metastases was a better predictor for overall response than either performance status or number of metastatic sites on presentation. Probability of response was significantly decreased by a raised serum carcinoembryonic antigen (CEA) and presence of peritoneal metastases. In liver metastases, a normal serum albumin was as significant a predictor for response as good performance status. The most important predictor for survival was initial performance status. The number of metastatic sites on presentation had no influence on survival. Site of metastasis can predict for response to 5FU-based chemotherapy and patients should be stratified according to the involved site of metastasis in the future.

Antimetabolites, Antineoplastic↗
PubMed1999

Adjuvant or palliative chemotherapy for colorectal cancer in patients 70 years or older.

PURPOSE: The surgical treatment of colorectal cancer (CRC) in elderly patients (age 70 years or older) has improved, but data on adjuvant and palliative chemotherapy tolerability and benefits in this growing population remain scarce. Elderly patients are underrepresented in clinical trials, and results for older patients are seldom reported separately. PATIENTS AND METHODS: Using a prospective database, we analyzed demographics, chemotherapy toxicity, response rates, failure-free survival (FFS), and overall survival (OS) of CRC patients receiving chemotherapy at the Royal Marsden Hospital. The cutoff age was 70 years. RESULTS: A total of 844 patients received first-line chemotherapy with various fluorouracil (5-FU)-containing regimens or raltitrexed for advanced disease, and 543 patients were administered adjuvant, protracted venous infusion 5-FU or bolus 5-FU/folinic acid (FA) chemotherapy. Of the 1,387 patients, 310 were 70 years or older. There was no difference in overall or severe (Common Toxicity Criteria III to IV) toxicity between the two age groups, with the exception of more frequent severe mucositis in older patients receiving adjuvant bolus 5-FU/FA. For patients receiving palliative chemotherapy, no difference in response rates (24% v 29%, P =.19) and median FFS (164 v 168 days) were detected when the elderly were compared with younger patients. Median OS was 292 days for the elderly group and 350 days for the younger patients (P =.04), and 1-year survival was 44% and 48%, respectively. The length of inpatient hospital stay was identical. CONCLUSION: Elderly patients with good performance status tolerated adjuvant and palliative chemotherapy for CRC as well as did younger patients and had similar benefits from palliative chemotherapy.

Adenocarcinoma↗
PubMed1998

Chemotherapy of oesophago-gastric cancer.

Oesophageal and gastric cancers are common tumors that represent a number of challenges for oncologists, gastroenterologists and surgeons. The prognosis remains poor with the majority of patients presenting with advanced disease. Combined chemotherapy and radiotherapy has demonstrated a survival benefit in patients with loco-regional oesophageal cancer compared to radiotherapy alone. In an interim analysis we have observed a 62% response rate using a chemoradiation regimen based on protracted venous infusion of 5-fluorouracil and cisplatin combined with radiotherapy in patients with inoperable oesophageal cancer. Improved outcomes with loco-regional disease has rekindled interest in preoperative therapy. In a trial comparing preoperative chemoradiation to surgery alone in patients with operable oesophageal adenocarcinoma, survival was improved with multimodality treatment. In addition, a study including both adeno- and squamous carcinomas demonstrated a trend towards improved survival. A complete pathological response to chemoradiation was associated with significantly improved survival. Gastric cancer is one of the most chemosensitive solid tumors of the gastrointestinal tract with the majority of patients being suitable for palliative chemotherapy. The ECF (epirubicin, cisplatin, protracted venous infusion 5-fluorouracil) regimen was developed in the Gastrointestinal unit of the Royal Marsden Hospital and first reported in 1991. In a prospective randomised trial including 274 patients ECF has been compared with the standard combination of 5-fluorouracil, adriamycin and methotrexate (FAMTX) in patients with previously untreated gastric cancer. Overall response rate, failure-free and overall survival were significantly improved with ECE, ECF also demonstrated improved quality of life and cost effectiveness when compared to the FAMTX regimen. ECF should now be regarded as the standard treatment for advanced oesophago-gastric cancer against which new therapies should be compared. In addition the Medical Research Council are conducting a trial randomising patients between surgery alone and perioperative chemotherapy using the ECF regimen in operable gastric cancer.

Antineoplastic Agents↗
PubMed1997

New approaches to the treatment of gastro-intestinal cancer.

A number of new cytotoxic agents are currently being assessed for the treatment of gastro-intestinal cancers. Colorectal cancer has been successfully treated with several direct thymidylate synthase inhibitors, oral 5-fluorouracil analogues, irinotecan, and oxaliplatin, alone and in combination regimens. Upper gastro-intestinal malignancies are also proving responsive to combinations including irinotecan and the taxanes. Pancreatic cancer, while remaining relatively chemoresistant, is proving treatable with the new direct thymidylate synthase inhibitors, docetaxel, and gemcitabine, improvements in quality of life being an important outcome. New strategies of treatment delivery are also proving beneficial. Neo-adjuvant chemotherapy is well tolerated for the treatment of gastric cancer and results in tumour downstaging. Randomized trials will show whether this translates into a survival advantage. Combination chemoradiation for oesophageal, pancreatic, and rectal cancers also appears to be an effective strategy. Biological therapies including hormonal manipulation, immunotherapy, angiogenesis inhibition, and gene-directed therapies are the subjects of intensive research at present, with many approaches being applied in early clinical trials. These have demonstrated the tolerability of many of these treatments with evidence for activity in some cases.

Chemotherapy, Adjuvant↗
PubMed1996

A changing Hausa diet.

We report results of a longitudinal study of shifting patterns of food consumption in a rural Hausa-Fulani village in northern Nigeria. While the broad outlines of diet did not change over the 12 years between two dietary surveys, important shifts occurred: a decline in the consumption of local cultigens, with a corresponding decrease in total caloric intake, as well as an embellishment of diet through the introduction of new foods. We suggest that this is best understood through the growing participation of this village in the wider economy. We juxtapose these dietary shifts to a model of disease risk that suggests, for the early period, that the coincidence of dietary elaboration and the periodicity of disease risk offered some degree of protection against malaria infection. For the more recent period, diet was no longer marked by conspicuous seasonal changes. To what extent these differences in diet patterns have affected the disease experience of this population is not yet clear.

Diet↗
PubMed1995

Optimising collection of autologous blood. A pilot study of the use of recombinant human erythropoietin and parenteral iron.

OBJECTIVE: To optimise collection of sufficient autologous blood for elective surgery. METHODS: Prospective study of 40 patients referred for donation of autologous blood, who were booked for elective orthopaedic surgery in the period August 1992 - September 1994. Patients received recombinant erythropoietin (r-EPO) to stimulate erythropoiesis, and sufficient iron by injection so that iron deficiency did not limit the bone marrow response to the r-EPO. RESULTS: Thirty-eight of the 40 patients treated with this protocol stored an average of 3.7 units each on a twice-weekly donation schedule. Only one patient required supplemental homologous blood (two units) in subsequent surgery. One patient developed persistent hypotension, and one a late reaction to parenteral iron (which was controlled with corticosteroids). There were no other adverse events. CONCLUSIONS: r-EPO in combination with parenteral iron is a safe and effective method of ensuring the collection of optimal amounts of autologous blood before surgery.

Adult↗
PubMed1995

Squamous oesophageal cancer can be downstaged using protracted venous infusion of 5-fluorouracil with epirubicin and cisplatin (ECF).

21 patients with squamous oesophageal carcinoma were treated with a new regimen designed in our unit and effective in treating gastric adenocarcinoma, consisting of continuous venous infusion of 5-fluorouracil for up to 24 weeks (200 mg/m2/day) with epirubicin (50 mg/m2) and cisplatin (60 mg/m2) every 3 weeks. 12 patients (57%) had an objective response. The median relapse free period was 7 months, median survival from start of chemotherapy 8.4 months, and median survival from diagnosis, 14 months. Symptomatic improvements were reported by 10/11 patients with pain (91%), 8/9 with anorexia (89%), 8/10 with reflux (80%) and 10/14 with dysphagia (71%). Grade 3 or 4 toxicity was reported by 11 patients: 5 had haematological toxicity, 3 vomiting, 2 infection and 1 diarrhoea. One patient developed peripheral neuropathy, 1 renal impairment and another peripheral vascular disease. Following chemotherapy, surgery was attempted in 5 patients. One remains well 3 years on, 2 had macroscopic clearance of tumour but died of postoperative complications. In 2, disease was irresectable. This regimen of moderate toxicity is effective at improving symptoms in the majority of patients. In some patients, tumours are briefly downstaged so that inoperable tumours may become operable.

Adult↗
PubMed1995

Conscious sedation: a quality management project.

Conscious sedation provides effective pain control and can relieve anxiety associated with procedures. The increased use of this modality has prompted the American Academy of Pediatrics to develop national guidelines that emphasize the need for patient monitoring to ensure patient safety. A policy was developed that incorporated continuous monitoring of patients and frequent documentation of physiological measures before, during, and after procedures. All procedures over a 2-month period in the outpatient (n = 19) and inpatient (n = 24) pediatric oncology units that required midazolam and fentanyl were retrospectively analyzed. A nonrandom sample of one third of the inpatient procedures (n = 8) was also observed to assess the dynamics of monitoring and recording. Procedures, including recovery time, lasted an average of 69 minutes, with longer recovery periods recorded for the outpatient unit. Nurses, particularly on the inpatient unit, were not always able to provide continuous monitoring through recovery because of the demands of other patient assignments. This study suggests that to realistically meet the needs of the patients and the institution's responsibility, the current guidelines may need to be reconsidered to allow more nursing discretion in patient monitoring and/or the nurse's patient care assignment must be more flexible to allow for changing demands.

Child↗
PubMed1995

Sociocultural factors in the use of prenatal care by Hmong women, Minneapolis.

Understanding the sociocultural context of prenatal care underuse by an immigrant population can suggest programmatic changes that result in more effective health care delivery. Ethnographic survey interviews of female Hmong clinic patients conducted in 1987/88 revealed that they objected to biomedical procedures and to being attended by several doctors; the women also reported poor communication with staff as a problem. Clinic reforms implemented in 1989/90 included hiring a nurse-midwife, reducing the number of pelvic examinations, expanding hours of operation, creating a direct telephone line to Hmong interpreters, and producing a Hmong-language prenatal health care education videotape. Women interviewed in 1993 reported a more positive clinic experience.

Adult↗