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Biomedical subjects

D Yip

Publications and source records attributed to D Yip.

At least 19 recordsLinked to original sources
PubMed2006

Chemotherapy and radiotherapy for inoperable advanced pancreatic cancer.

BACKGROUND: Pancreatic cancer has a poor prognosis. The benefit of chemotherapy, radiotherapy or both as a palliative treatment of advanced or relapsed disease is uncertain. OBJECTIVES: To assess the effects of chemotherapy and/or radiotherapy in the management of pancreatic adenocarcinoma in people with inoperable advanced disease. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which includes the Cochrane Upper Gastrointestinal and Pancreatic Diseases (UGPD) Group Trials Register (The Cochrane Library 2005, Issue 1); CANCERLIT (1975-2002); MEDLINE (1966 to January 2005); and EMBASE (1980 to January 2005). We handsearched reference lists from trials revealed by electronic searches to identify further relevant trials. We searched published abstracts from relevant conference proceedings. We contacted colleagues and experts in the field, and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. SELECTION CRITERIA: Randomised controlled trials (single- or double-blind) in patients with advanced inoperable pancreatic cancer, in which one of the intervention types (chemotherapy or radiotherapy) was contrasted with either placebo or another type of intervention. Studies comparing non-chemotherapy agents such as biological agents, hormones, immunostimulants, vaccines and cytokines were excluded. DATA COLLECTION AND ANALYSIS: Studies were assessed for eligibility and quality. Data were extracted by groups of two independent reviewers, with conflicts resolved by a third reviewer. Study authors were contacted for more information. MAIN RESULTS: Fifty trials (7043 participants) were included. Chemotherapy significantly reduced the one-year mortality (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.25 to 0.57, P value < 0.00001) when compared to best supportive care. Also, chemoradiation improved one year survival (0% versus 58%, P value 0.001) when compared to best supportive care. There was no significant difference in one-year mortality for 5FU alone versus 5FU combinations (OR 0.90, 95% CI 0.62 to 1.30); single-agent chemotherapy versus gemcitabine (OR 1.34, 95% CI 0.88 to 2.02, P value 0.17); or gemcitabine alone versus gemcitabine combinations (OR 0.88, 95% CI 0.74 to 1.05). However, subgroup analysis showed that platinum-gemcitabine combinations reduced six-month mortality compared to gemcitabine alone (OR 0.59, 95% CI 0.43 to 0.81, P value 0.001). A qualitative overview suggested that chemoradiation produced better survivals than either best supportive care or radiotherapy. Chemoradiation treatment was associated with more toxicity. AUTHORS' CONCLUSIONS: Chemotherapy appears to prolong survival in people with advanced pancreatic cancer and can confer clinical benefits and improve quality of life. Combination chemotherapy did not improve overall survival compared to single-agent chemotherapy. Gemcitabine is an acceptable control arm for future trials investigating scheduling and combinations with novel agents. There is insufficient evidence to recommend chemoradiation in patients with locally advanced inoperable pancreatic cancer as a superior alternative to chemotherapy alone.

Antineoplastic Agents↗
PubMed2006

Gemcitabine and oxaliplatin followed by paclitaxel and carboplatin as first line therapy for patients with suboptimally debulked, advanced epithelial ovarian cancer. A phase II trial of sequential doublets. The GO-First Study.

OBJECTIVES: Gemcitabine and oxaliplatin are active in epithelial ovarian cancer with minimal overlapping toxicity. We studied the efficacy and toxicity of this combination in patients with advanced ovarian cancer when given prior to carboplatin and paclitaxel. METHODS: Chemonaive patients with epithelial ovarian cancer and measurable disease were eligible for the study. Treatment consisted of gemcitabine 1250 mg/m2 on days 1 and 8 and oxaliplatin 130 mg/m2 on day 8 every 21 days (GO) for 4 cycles. This was followed by carboplatin AUC = 6 and paclitaxel 175 mg/m2 on day 1 every 21 days (CP) for 4 cycles. RESULTS: Twenty patients, median age 62 years (range 39-78), FIGO stages III (16) and IV (4) received treatment. The response rate (RR) after 4 cycles of GO was 80% (95%CI 61-99%) (4 complete responses (CR), 12 partial responses (PR)). Interval debulking surgery was performed in 7 patients (35%). After CP chemotherapy, RR increased to 85% (95%CI 68-100%) (CR = 13, PR = 4). Median time to progression was 14.5 months. Estimated median overall survival was 31.5 months. Toxicities of GO were mild; grade 3/4 nausea in 3 patients (15%) and vomiting in 2 patients (10%), grade 3/4 neutropenia in 5 patients (25%). Grade 2/3 peripheral neuropathy occurred in 5 patients (25%). After sequential administration of CP, grade 2/3 neuropathy occurred in 13 patients (72%). CONCLUSION: The sequential doublet regimen of GO followed by CP resulted in unacceptable neurotoxicity and is not recommended for further study; however, the doublet gemcitabine and oxaliplatin has significant activity in the first line treatment of patients with ovarian cancer.

Adult↗
PubMed2005

A prospective evaluation of treatment with Selective Internal Radiation Therapy (SIR-spheres) in patients with unresectable liver metastases from colorectal cancer previously treated with 5-FU based chemotherapy.

BACKGROUND: To prospectively evaluate the efficacy and safety of Selective Internal Radiation (SIR) spheres in patients with inoperable liver metastases from colorectal cancer who have failed 5FU based chemotherapy. METHODS: Patients were prospectively enrolled at three Australian centres. All patients had previously received 5-FU based chemotherapy for metastatic colorectal cancer. Patients were ECOG 0-2 and had liver dominant or liver only disease. Concurrent 5-FU was given at investigator discretion. RESULTS: Thirty patients were treated between January 2002 and March 2004. As of July 2004 the median follow-up is 18.3 months. Median patient age was 61.7 years (range 36-77). Twenty-nine patients are evaluable for toxicity and response. There were 10 partial responses (33%), with the median duration of response being 8.3 months (range 2-18) and median time to progression of 5.3 mths. Response rates were lower (21%) and progression free survival shorter (3.9 mths) in patients that had received all standard chemotherapy options (n = 14). No responses were seen in patients with a poor performance status (n = 3) or extrahepatic disease (n = 6). Overall treatment related toxicity was acceptable, however significant late toxicity included 4 cases of gastric ulceration. CONCLUSION: In patients with metastatic colorectal cancer that have previously received treatment with 5-FU based chemotherapy, treatment with SIR-spheres has demonstrated encouraging activity. Further studies are required to better define the subsets of patients most likely to respond.

Adult↗
PubMed2005

Prospective study of treatment with selective internal radiation therapy spheres in patients with unresectable primary or secondary hepatic malignancies.

AIM: To prospectively evaluate the efficacy and safety of Selective Internal Radiation (SIR) Spheres (Sirtex Medical, Sydney, NSW, Australia) in patients with unresectable primary or secondary hepatic malignancies. METHODS: We report our experience of SIR sphere therapy at three Australian centres. Patients with previously untreated colorectal cancer (CRC) received concurrent 5FU, other patients with CRC received 5-FU at investigator discretion and all other patients received SIR spheres alone. RESULTS: Forty-six patients were enrolled between January 2002 and June 2003. The majority (32 patients) had metastatic colorectal cancer and five patients had hepatocellular carcinoma. The median age of patients was 64 years (range 46-78 years). Forty-three patients were evaluable for response. There were 12 partial responses, of which 10 were in patients with CRC. The median duration of response for all patients was 8.6 months (range 2-21 months). Overall treatment related toxicity was acceptable. Significant late toxicity included four cases of severe gastric ulceration, despite standard work-up and treatment by experienced interventional radiologists. CONCLUSION: In this series of patients, treatment with SIR-spheres has demonstrated modest activity, mostly observed in patients with CRC. Toxicity was substantial in a small number of patients.

Adenocarcinoma↗
PubMed2003

A dose-escalating study of oral eniluracil/5-fluorouracil plus oxaliplatin in patients with advanced gastrointestinal malignancies.

BACKGROUND: Oral eniluracil/5-fluorouracil (5-FU) was shown in early clinical studies to have promising activity against gastrointestinal malignancies. Oxaliplatin in combination with 5-FU also has activity against these tumour types. The primary objective of this study was to determine a tolerable dose for oral eniluracil/5-FU in combination with oxaliplatin. PATIENTS AND METHODS: Twenty-three patients with advanced gastrointestinal malignancies were recruited into this open-label study. Patients received a fixed dose of oxaliplatin (130 mg/m(2) on the first day of a 21-day cycle), and the dose intensity of oral eniluracil/5-FU was gradually increased by escalating the number of days of treatment per course. RESULTS: The maximum tolerated dose intensity was eniluracil/5-FU 10.0/1.0 mg/m(2) twice daily for 16 days in combination with oxaliplatin 130 mg/m(2) on the first day of a 21-day cycle. Dose-limiting toxicities included vomiting and diarrhoea. The objective tumour response rate was 26% with a median duration of response of 15.3 weeks (95% confidence interval 8.5-22.1). Twenty-two patients (96%) experienced neurotoxicity (sensory neuropathy or cold-related dysaesthesia), although only two events were severe (grade 3). CONCLUSIONS: The recommended dose for future study in patients with advanced gastrointestinal cancer is 10.0/1.0 mg/m(2) oral eniluracil/5-FU twice daily for 14 days in combination with oxaliplatin 130 mg/m(2) on the first day of each treatment cycle.

Administration, Oral↗
PubMed2002

Subcutaneous chest ports via the internal jugular vein. A retrospective study of 117 oncology patients.

PURPOSE: To review image-guided chest port insertion using the right internal jugular vein as the access site of choice. MATERIAL AND METHODS: One hundred and eighteen subcutaneous chest ports were placed via the internal jugular vein in 117 patients with malignancies using both fluoroscopic and US guidance in interventional radiology suites. RESULTS: The technical success rate was 100% with no procedural complications. Follow-up was obtained in all patients with total access days of 40,450 days (mean, 342.8 days). Premature catheter removal was required in 8 patients (6.8%, 0.20 per 1,000 access days) due to non-treatable complications: 2 catheter occlusions/malfunctions (1.7%, 0.05 per 1,000 access days), 1 catheter-related skin erosion (0.85%, 0.024 per 1,000 access days), and 5 infections (4.2%, 0.15 per 1,000 access days). Two symptomatic right upper extremity venous thromboses also occurred (1.7%, 0.05 per 1,000 access days) that were treated successfully with anticoagulation. CONCLUSION: Image-guided placement of internal jugular vein chest ports has a high success rate and low complication rate compared with reported series of unguided subclavian vein port insertion. The internal jugular vein should be used as the preferred venous access site compared to the subclavian vein.

Catheterization, Central Venous↗
PubMed2001

A phase II study evaluating the tolerability and efficacy of CAELYX (liposomal doxorubicin, Doxil) in the treatment of unresectable pancreatic carcinoma.

BACKGROUND: Preclinical studies of liposomal doxorubicin (CAELYX) have demonstrated significant inhibition of growth of human pancreatic cancer explants in nude mice. This study evaluated the efficacy of CAELYX in chemotherapy-naïve patients with unresectable, histologically confirmed pancreatic carcinoma. Secondary endpoints were quality of life (QOL). time to progression and overall survival. PATIENTS AND METHODS: Twenty-two patients (median age 65) were enrolled. CAELYX was administered to the first five patients at a dose of 30 mg/m2 three-weekly. Two of these patients were dose escalated to 50 mg/m2 four-weekly. Subsequent patients were all treated on the latter schedule. RESULTS: Two patients died after consenting to enter the study but before treatment was commenced and are not included in the analysis. Sixteen patients were evaluable for response. No objective responses were seen. Six patients had stable disease. One patient experienced grade 4 toxicity with palmar plantar dysaesthesia (PPE), but continued treatment after dose reduction and delay. Four patients experienced grade 3 stomatitis and two grade 3 nausea. Median survival from time of starting chemotherapy was 3.2 months (range 21 days to 19 months) and one year survival was 10%. Eight patients completed at least two EORTC QLQ C-30 questionnaires. There was no significant change in either global QOL or in any functional or symptom subscale score. CONCLUSION: No objective responses were seen with CAELYX in this study. CAELYX was however associated with stable disease, but data were inconclusive with regard to clinical benefit. It warrants further investigation in the context of combination trials.

Aged↗
PubMed2001

PET and PLAP in suspected testicular cancer relapse: beware sarcoidosis.

A 31-year-old man previously treated with chemotherapy for metastatic testicular cancer presented with new mediastinal lymphadenopathy and peripheral lung opacities. Serum tumour markers were not elevated and a PET (positron emission tomography) scan revealed increased FDG (fluoro-deoxyglucose) uptake in the lungs and mediastinum consistent with testis cancer relapse. A biopsy of a mediastinal lymph node was performed and the pathology was that of sarcoidosis. Immunohistochemistry however was positive for PLAP (placental alkaline phosphatase) and negative for EMA (epithelial membrane antigen). This immunohistochemical profile raised concerns that the observed pathology represented a sarcoid reaction to micro-metastatic testicular cancer relapse. We performed immunohistochemical pathology analysis on four known cases of sarcoidosis and found the same immunohistochemical-staining pattern. This case highlights the problem of specificity when interpreting the significance of PET scans and immunohistochemical analysis in this situation. Sarcoidosis, a condition that has been associated with testicular cancer, should always be considered in the differential diagnosis.

Adult↗
PubMed2001

Charnley total hip arthroplasty in Chinese patients less than 40 years old.

Forty-seven total hip arthroplasties were reviewed in 33 Chinese patients who were <40 years old at the time of operation. The preoperative diagnosis was avascular necrosis in 40% of the hips. A Charnley prosthesis was inserted using early cementing techniques in every hip. The average follow-up was 14.9 years (range, 6.9-21.1 years). The mean preoperative Harris hip score was 43.8 (range, 26-74), and the mean score at latest follow-up was 87.7 (range, 74-99) for the surviving hips. Thirty hips (63%) were revised, and 1 hip was removed because of late deep infection. The main cause of failure was aseptic loosening of the acetabular component. Using revision and radiologic loosening as endpoints, the cumulative survival rate for the acetabular component was 86.3% at 10 years and 27.0% at 15 years. The survival of the femoral components was 81.3% at 15 years. Patients with avascular necrosis had a higher failure rate than patients with other diagnoses (P =.001). An area of cement mantle that was <2 mm thick affected adversely the survival rate of the acetabular components (P =.04).

Adolescent↗
PubMed2001

Epirubicin, cisplatin, and prolonged or brief infusional 5-fluorouracil in the treatment of carcinoma of unknown primary site.

The cytotoxic regimen of epirubicin, cisplatin, and continuous infusional 5-fluorouracil (ECF) has demonstrated activity in a range of malignancies, including gastroesophageal, breast, and pancreatic cancers. Prolonged infusional central venous catheter (CVC) mediated therapy is not always feasible and modifications of the 5-fluorouracil (5FU) schedule have been reported. We reviewed our experience of both the standard and a modified ECF regimen in patients diagnosed with carcinoma of unknown primary site (CUPS). A retrospective analysis of all patients diagnosed with CUPS (31 adenocarcinoma and 5 poorly differentiated carcinoma) and treated with ECF between June 1994 and June 1998 was undertaken. Thirty-six patients, median age 56 (range: 24-74), were treated thrice-weekly with 50 mg/m2 epirubicin, 60 mg/m2 cisplatin, and 5-FU administered either by continuous infusion 200 mg/m2/d via a CVC (standard ECF) or as a 6-h infusion 600 mg/m2 through a peripheral venous catheter (modified ECF). Thirteen patients were treated with standard ECF and 23 received modified ECF. The median number of cycles administered was 4 (range: 1-10). Thirty-two patients had evaluable disease, seven (22%; 95% confidence interval: 8-36%) demonstrated a partial response, including three patients that received standard ECF and four treated with modified ECF. There were no complete responses. The median survival for all 36 patients was 9.0 mo. Median survival for patients treated with standard ECF was 11.7 mo as compared to 5.1 mo for the modified ECF schedule (p = 0.052). Liver involvement and elevation of serum CA19.9 were identified as possible adverse prognostic factors. Both regimens were well tolerated, with the only grade 3/4 toxicity recorded being leukopenia (four patients), nausea/vomiting (seven patients), and diarrhea (one patient). CVC complications in the standard ECF group were thrombosis (one patient) and infection (three patients). There were no treatment-related deaths. We conclude that ECF, whether modified or standard, has modest activity in the setting of CUPS. Patient survival is comparable to survival documented in previous reports of CUPS treatment. The apparent survival difference between the two ECF schedules may be the result of patient selection factors. The optimal treatment of CUPS remains unknown and can only be determined through randomized controlled trials.

Adenocarcinoma↗
PubMed2001

Management of small cell lung cancer.

Small cell lung cancer is a tumor that has a very poor prognosis without treatment. It is however, highly responsive to chemotherapy and radiotherapy. Pretreatment clinical and laboratory parameters--in addition to staging--can prognosticate outcome and help define the aim of treatment. Different schedules of chemotherapy have been developed and varied strategies, such as chemotherapy dose intensification have been tried to improve outcomes. New agents, such as irinotecan, gemcitabine and topotecan have also been tested. Clinical trials have helped to define strategies of integrating thoracic radiotherapy and prophylactic cranial radiotherapy into management of those patients with limited disease to improve survival further. Despite good initial responses to treatment, most patients eventually relapse. Maintenance strategies with ongoing chemotherapy or novel agents, such as interferon, matrix metalloproteinase inhibitors, thalidomide and vaccines are discussed.

Antineoplastic Agents↗
PubMed2000

Predictive and prognostic factors in small cell lung cancer: current status.

Clinical and laboratory parameters can predict response to chemotherapy and long term survival in small cell lung cancer, and may predict those at risk of early treatment related toxicity. This paper reviews the predictive models that have been developed to divide patients into prognostic groups for response and survival on the basis of clinical and laboratory parameters. These factors may be used for the stratification of patients in clinical trials and to help clinicians make appropriate treatment decisions for individual patients. A number of treatment-related factors can also affect outcomes. The evidence for interventions to prevent treatment deaths in high risk patients, such as prophylactic antibiotics, dosage modification or colony stimulating factor support are also reviewed.

Antineoplastic Agents↗
PubMed2000

Local recurrence after mastectomy and adjuvant CMF: implications for adjuvant radiation therapy.

BACKGROUND: The purpose of the present study was to evaluate the patterns of failure in a series of patients with node-positive breast cancer that was treated by total mastectomy and adjuvant chemotherapy. METHODS: A retrospective review was undertaken of 217 patients with node-positive breast cancer who were referred to the oncology departments of Westmead and Nepean Hospitals following total mastectomy between January 1980 and December 1991. The majority of patients (82%) were pre- or peri-menopausal and all underwent chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) by either an oral or intravenous regimen. No patient received adjuvant radiation therapy. RESULTS: After a median follow up of 8.7 years, 19% of patients had developed a loco-regional recurrence (LRR). The majority of LRR (79%) occurred within the initial 3 years after mastectomy. The risk of LRR was positively associated with the size of the tumour (11% for T1 vs 53% for T3, P < 0.001) and axillary nodal status (16% for three or fewer positive nodes vs 31% for four or more positive nodes, P = 0.017). Patients with T1 or T2 tumours and 1-3 positive nodes had the lowest rate of LRR (11%) while those with T3 tumours or 4-10 positive nodes had the highest rates, ranging from 23 to 75%. Relapse at the chest wall and supraclavicular fossa (SCF) accounted for 46 and 35%, respectively, of all LRR; relapse at the internal mammary chain and axilla was uncommon. CONCLUSION: The data suggest that patients with T3 tumours (> 5 cm) and any nodal involvement or patients with four or more involved axillary nodes, regardless of T stage, are at a high risk of LRR and will benefit from adjuvant radiation therapy to the chest wall and SCF.

Adult↗
PubMed2000

Immunomodulation therapy in colorectal carcinoma.

There has been much progress in the understanding of the relationship between the immune system and colorectal cancer. This has led to the use of immunomodulatory therapy in the adjuvant and palliative treatment of the condition. Although attempts at the use of non-specific immunomodulation with agents such as levamisole, cimetidine, alpha interferon and Bacillus Calmette-Guerin (BCG) have not produced significant clinical benefits when tested in randomized trials in both the adjuvant setting and for metastatic disease, promising results are being obtained with more specific therapy. Edrecolomab [corrected], a murine monoclonal antibody targeting the 17-1A antigen on malignant colorectal cells has produced a reduction in relapse and mortality rates when used as adjuvant treatment following surgery for Dukes' C colon cancer. Active specific therapy with autologous tumour vaccine administered with BCG has produced similar benefits in Dukes' B cancer. Both 3H1 anti-idiotypic antibody against carcinoembryonic antigen and 105AD7 antibody to gp72 glycoprotein have demonstrated in-vitro and in-vivo immune activation against tumour. Non-randomized studies postulate prolongation of survival using these antibodies in advanced disease. These agents are all currently being tested in randomized studies powered to detect meaningful survival differences and clinical benefit. Immune therapy offers the potential of low toxicity therapy in colorectal cancer and may have a role as an adjunct to conventional chemotherapy.

Adjuvants, Immunologic↗
PubMed1999

Colorectal cancer.

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Antineoplastic Agents↗