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Ian F Tannock

Publications and source records attributed to Ian F Tannock.

At least 37 records · Page 2Linked to original sources
PubMed2005

Repopulation of cancer cells during therapy: an important cause of treatment failure.

Radiotherapy and chemotherapy are given in multiple doses, which are spaced out to allow the recovery of normal tissues between treatments. However, surviving cancer cells also proliferate during the intervals between treatments and this process of repopulation is an important cause of treatment failure. Strategies developed to overcome repopulation have improved clinical outcomes, and now new strategies to inhibit repopulation are emerging in parallel with advances in the understanding of underlying biological mechanisms.

Antineoplastic Agents↗
PubMed2004

Tolerability of the Intergroup 0099 (INT 0099) regimen in locally advanced nasopharyngeal cancer with a focus on patients' nutritional status.

PURPOSE: The Intergroup 0099 trial (INT 0099) for locally advanced nasopharyngeal cancer (NPC) has set a standard of practice. This retrospective review documents our institutional experience with this regimen. METHODS AND MATERIALS: For all NPC patients treated between January 1998 and December 2002 with the INT 0099 regimen, compliance, toxicity, weight change, and feeding tube use were recorded. Patients were grouped by therapy completion status and by feeding tube status. RESULTS: Of 78 consecutive patients, 75 were evaluable. Compliance with radiotherapy was excellent. Only 43% and 61% of patients received all cycles of concurrent and adjuvant chemotherapy, respectively. Patients who successfully completed therapy had a higher average baseline weight and were more likely to have had a prophylactic feeding tube. Forty of 75 patients had a feeding tube inserted and were analyzed as two groups. Patients with prophylactic insertion (n = 23) had a more gradual drop in weight, and recovered to a greater degree at 1 year (93.6% vs. 87.2%), than those with a feeding tube inserted therapeutically during treatment (n = 17). CONCLUSIONS: The INT 0099 regimen was generally delivered with modifications to the chemotherapy component, as in the original trial. The prophylactic insertion of a feeding tube may facilitate therapy completion and weight recovery in some patients.

Adolescent↗
PubMed2004

Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer.

BACKGROUND: Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced, hormone-refractory prostate cancer, but it does not improve survival. We compared such treatment with docetaxel plus prednisone in men with this disease. METHODS: From March 2000 through June 2002, 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and were randomly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks, 75 mg of docetaxel per square meter every three weeks, or 30 mg of docetaxel per square meter weekly for five of every six weeks. The primary end point was overall survival. Secondary end points were pain, prostate-specific antigen (PSA) levels, and the quality of life. All statistical comparisons were against mitoxantrone. RESULTS: As compared with the men in the mitoxantrone group, men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 (95 percent confidence interval, 0.62 to 0.94; P=0.009 by the stratified log-rank test) and those given weekly docetaxel had a hazard ratio for death of 0.91 (95 percent confidence interval, 0.75 to 1.11; P=0.36). The median survival was 16.5 months in the mitoxantrone group, 18.9 months in the group given docetaxel every 3 weeks, and 17.4 months in the group given weekly docetaxel. Among these three groups, 32 percent, 45 percent, and 48 percent of men, respectively, had at least a 50 percent decrease in the serum PSA level (P<0.001 for both comparisons with mitoxantrone); 22 percent, 35 percent (P=0.01), and 31 percent (P=0.08) had predefined reductions in pain; and 13 percent, 22 percent (P=0.009), and 23 percent (P=0.005) had improvements in the quality of life. Adverse events were also more common in the groups that received docetaxel. CONCLUSIONS: When given with prednisone, treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain, serum PSA level, and quality of life, as compared with mitoxantrone plus prednisone.

Adenocarcinoma↗
PubMed2004

Cognitive impairment associated with chemotherapy for cancer: report of a workshop.

Cognitive dysfunction may occur in some patients who receive chemotherapy. We provide a summary of an April 2003 workshop on this topic, that included medical oncologists, radiologists, clinical and experimental psychologists, and patient advocates. Current studies indicate that cognitive deficits are often subtle, although they are observed consistently in a proportion of patients, may be durable, and can be disabling. Deficits have been observed in a range of cognitive functions. Underlying mechanisms are unknown, although preliminary studies suggest there may be genetic predisposition and that cognitive impairment may be accompanied by changes in the brain detectable by neuroimaging. The following priorities were established for future research: (1) large-scale clinical studies that use both a longitudinal design and concurrent evaluation of patients with cancer who do not receive chemotherapy-such studies should address the probability and magnitude of cognitive deficits, factors that predict them, and underlying mechanisms; (2) exploration of discrepancies between subjective reports of cognitive dysfunction and the objective results of cognitive testing; (3) studies of cognitive function in patients receiving treatment for diseases other than breast cancer, and in both men and women, to address the hypothesis that underlying mechanisms relate to changes in serum levels of sex hormones and/or to chemotherapy-induced menopause; (4) development of interventions to alleviate these problems; and (5) development of animal models and the use of imaging techniques to address mechanisms that might cause cognitive impairment associated with chemotherapy.

Antineoplastic Agents↗
PubMed2004

Quality of abstracts describing randomized trials in the proceedings of American Society of Clinical Oncology meetings: guidelines for improved reporting.

PURPOSE: To evaluate the quality of reporting in abstracts describing randomized controlled trials (RCTs) included in the Proceedings of American Society of Clinical Oncology (ASCO) meetings and to propose reporting guidelines for abstracts that are submitted to future meetings. METHODS: Guidelines for reporting of RCTs in abstracts were developed by extracting key elements from published guidelines for full reports of RCTs, and modified based on an expert survey. Abstracts presenting results of RCTs with sample size > or = 200 were identified from the ASCO Proceedings for the years 1989 to 1998. Information regarding the quality of each abstract was extracted, and a quality score (possible range, 0 to 10) was assigned based on adherence to the guidelines. RESULTS: Brief description of the intervention, explicit identification of the primary end point, and presentation of results accompanied by statistical tests were regarded by experts as the most important items to include in an abstract, whereas presentation of secondary and subgroup analyses was the least important. Deficiencies in reporting were present in almost all of the 510 abstracts; for example, only 22% of the abstracts provided explicit identification of the primary end point. The median quality score was 5.5 (range, 2.0 to 8.5); the quality score improved with time (P <.0001) and was better for oral or plenary presentations (P =.0003). CONCLUSION: The quality of reporting of RCTs in abstracts submitted to Annual Meetings of ASCO is suboptimal. Although space precludes the inclusion of details required in the final report, abstracts could be improved through the use of explicit minimal guidelines, which are suggested in this article.

Abstracting and Indexing↗
PubMed2004

Low-dose prophylactic platelet transfusions in recipients of an autologous peripheral blood progenitor cell transplant and patients with acute leukemia: a randomized controlled trial with a sequential Bayesian design.

BACKGROUND: Prophylactic platelet (PLT) transfusions are standard treatment for patients receiving high-dose chemotherapy, but the optimal dose is not known. A randomized controlled trial was undertaken to examine the effectiveness of low-dose PLT transfusions and to determine the need for further studies. STUDY DESIGN AND METHODS: Patients (n = 111) with acute leukemia or undergoing autologous peripheral blood progenitor cell (PBPC) transplantation were randomly assigned to receive low-dose (3 PLT units) or standard-dose (5 PLT units) prophylactic PLT transfusions and were monitored daily for bleeding. Using a sequential Bayesian design, the difference in major bleeding events was determined. RESULTS: The percentage of patients with major bleeding events was 10.7 percent (95% credible region, 5.1%-21.2%) in the low-dose PLT group and 7.3 percent (95% credible region, 2.9%-17.2%) in the standard-dose PLT group. The two additional events in the low-dose group occurred when the PLT count exceeded 100 x 10(9) per L. There is an 89 percent probability that the absolute increase in major bleeds is less than 10 percent with low-dose PLT transfusions. The number of minor bleeding events was higher in the standard-dose group. Patients receiving low-dose PLT transfusions received 25 percent fewer PLT units. There was an 89 percent probability that low-dose transfusions reduced PLT utilization in patients with acute leukemia and a 60 percent probability in patients undergoing PBPC transplantation. CONCLUSION: Low-dose PLT transfusions appear to be safe and effective and reduce PLT utilization. They should be further evaluated in clinical trials designed to evaluate equivalency.

Acute Disease↗
PubMed2003

Cognitive function, fatigue, and menopausal symptoms in women receiving adjuvant chemotherapy for breast cancer.

PURPOSE: There is evidence that cognitive dysfunction, fatigue, and menopausal symptoms may occur in women receiving adjuvant chemotherapy for breast cancer. Here, we determine their incidence and severity, and interrelationships between them and quality of life. PATIENTS AND METHODS: In this study, 110 women receiving adjuvant chemotherapy each nominated a female relative, friend, or neighbor (matched by age) as a control; 100 eligible matched pairs were evaluated. Patients and controls completed the following assessments: the High-Sensitivity Cognitive Screen, and the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life scale with subscales for fatigue (FACT-F) and endocrine symptoms (FACT-ES). They also performed tests of attention and reaction time. RESULTS: Patients and controls were well matched for age and level of education. There was a higher incidence of moderate or severe cognitive impairment in the patient group (16% v 4%; P =.008). Patients experienced much more fatigue than controls (median FACT-F scores, 31 v 46; P <.0001) and more menopausal symptoms (median FACT-ES scores, 58 v 64; P <.0001). Self-reported quality of life of the patients was poorer than for controls, especially in physical and functional domains (median FACT-G scores, 77 v 93; P <.0001). There was strong correlation between fatigue, menopausal symptoms, and quality of life (P <.0001 for each pair), but none were significantly associated with the presence of cognitive dysfunction. CONCLUSION: Adjuvant chemotherapy causes cognitive dysfunction, fatigue, and menopausal symptoms in women with breast cancer. Priority should be given to the study of strategies that might reduce these toxic effects.

Adult↗
PubMed2003

Selective estrogen receptor modulators as inhibitors of repopulation of human breast cancer cell lines after chemotherapy.

PURPOSE: Repopulation of surviving tumor cells between courses of chemotherapy might lead to effective drug resistance. Here we study inhibition of repopulation of hormone-responsive human breast cancer cell lines by selective estrogen receptor (ER) modulators (SERMs) during courses of chemotherapy. EXPERIMENTAL DESIGN: Hormone responsive breast cancer cell lines MCF-7 and T47D, and the ER- cell line MDA-231, were treated with either 4-hydroxy tamoxifen (4OHT) or arzoxifene during weekly courses of treatment with 5-fluorouracil (5-FU) or methotrexate (MTX). Clonogenic assays were performed to determine the overall survival of tumor cells after treatment with the SERMs alone, after one to three doses of 5-FU or MTX alone, and after 5-FU or MTX followed by each of the SERMs. RESULTS: Both SERMs inhibited the growth of ER+ cells MCF-7 and T47D but had no effect on the ER-cell line MDA-231. Arzoxifene was more effective than 4OHT. Between courses of treatment with either 5-FU or MTX, repopulation of ER+ cells was specifically inhibited by the SERMs, whereas repopulation of ER- MDA-231 was not affected. CONCLUSIONS: Arzoxifene and 4OHT can inhibit specifically the repopulation of ER+ breast cancer cells between courses of chemotherapy. Scheduling of short-acting SERMs between courses of chemotherapy has the potential to improve therapeutic index.

Antineoplastic Agents, Hormonal↗
PubMed2003

Factors associated with failure to publish large randomized trials presented at an oncology meeting.

CONTEXT: Large clinical trials are the criterion standard for making treatment decisions, and nonpublication of the results of such trials can lead to bias in the literature and contribute to inappropriate medical decisions. OBJECTIVES: To determine the rate of full publication of large randomized trials presented at annual meetings of the American Society of Clinical Oncology (ASCO), quantify bias against publishing nonsignificant results, and identify factors associated with time to publication. DESIGN: Survey of 510 abstracts from large (sample size, > or =200), phase 3, randomized controlled trials presented at ASCO meetings between 1989 and 1998. Trial results were classified as significant (P< or =.05 for the primary outcome measure) or nonsignificant (P>.05 or not reported), and the type of presentation and sponsorship were identified. Subsequent full publication was identified using a search of MEDLINE and EMBASE, completed November 1, 2001; the search was updated in November 2002, using the Cochrane Register of Controlled Trials. Authors were contacted if the searches did not find evidence of publication. MAIN OUTCOME MEASURES: Publication rate at 5 years; time from presentation to full publication. RESULTS: Of 510 randomized trials, 26% were not published in full within 5 years after presentation at the meeting. Eighty-one percent of the studies with significant results had been published by this time compared with 68% of the studies with nonsignificant results (P<.001). Studies with oral or plenary presentation were published sooner than those not presented (P =.002), and studies with pharmaceutical sponsorship were published sooner than studies with cooperative group sponsorship or studies for which sponsorship was not specified (P =.02). These factors remained significant in a multivariable model. The most frequent reason cited by authors for not publishing was lack of time, funds, or other resources. CONCLUSIONS: A substantial number of large phase 3 trials presented at an international oncology meeting remain unpublished 5 years after presentation. Bias against publishing nonsignificant results is a problem even for large randomized trials. Nonpublication breaks the contract that investigators make with trial participants, funding agencies, and ethics boards.

Bias↗
PubMed2003

Repopulation in murine breast tumors during and after sequential treatments with cyclophosphamide and 5-fluorouracil.

The rate of repopulation of surviving cells increases during fractionated radiotherapy and limits the ability to control tumors. Repopulation is likely to be more important during the longer intervals between courses of chemotherapy and is a potential cause of clinical resistance to chemotherapy. To evaluate the rate of repopulation of surviving cells in MXT and EMT-6 mouse breast tumors between successive cycles of chemotherapy, tumor-bearing mice were treated with up to three weekly cycles of cyclophosphamide or 5-fluorouracil (5FU). Animals were killed at different intervals during and after chemotherapy, and uptake of 5'bromodeoxyuridine and immunohistochemical staining were selected to study repopulation. When tumors regrew after a single treatment, the proliferative rate of tumor cells returned to control values. During successive courses of chemotherapy, the proliferative rate of surviving cells increased in both tumors, e.g., in 5FU-treated MXT tumors, the percentages of 5'bromodeoxyuridine-labeled proliferating cells at 7 days after the first, second, and third treatment were 25 +/- 12%, 29 +/- 9%, and 27 +/- 11%; it was 32 +/- 6% at 14 days after the third treatment. The corresponding value in control tumors was 19 +/- 2% (P < 0.05 for each comparison). Accelerating repopulation after sequential treatments with cyclophosphamide or 5FU can lead to effective drug resistance in the absence of changes in the sensitivity of constituent cells.

Animals↗
PubMed2003

Placebo effects in oncology.

BACKGROUND: Previous studies have suggested that placebo treatment can have positive effects on a variety of disorders and disease-related symptoms. However, the methodology used to collect and interpret the data may not have been ideal, because the studies were not double-blinded or the endpoints were not properly validated. The purpose of the present study was to determine the probability of improvement in symptoms or quality of life and tumor response in cancer patients treated with placebos in randomized controlled trials. We hypothesized that administration of placebos would improve symptom control and quality of life but would not lead to tumor response. METHODS: We reviewed reports of randomized controlled trials in which there was a placebo arm (37 trials) or a best supportive care (BSC) arm (10 trials). RESULTS: In trials that assessed average responses for patients in the placebo arm, improvements in average levels of pain were reported in two of six trials and in appetite, in one of seven trials. No improvements in average levels of weight gain (six trials), in quality of life (as assessed by patients; 10 trials), or in performance status (as assessed by physicians; nine trials) were reported. In trials that assessed response to a placebo in individual patients, 0%-21% of patients showed reduced pain or decreased analgesic intake, 8%-27% of patients showed appetite improvement, 7%-17% of patients showed weight gain, and 6%-14% of patients showed improvement in performance status. Quality of life for individual patients was not reported in any trial. Tumor response assessed by World Health Organization criteria was observed in 10 (2.7%) of 375 patients (seven trials total). Response as assessed by a serum marker was observed in 1 (1.7%) of 60 patients (two trials total). The probability of symptom improvement in patients receiving BSC was generally similar to that in patients receiving placebo, although no improvement in pain and only one tumor response among 191 patients (five trials) were reported. CONCLUSION: In randomized double-blinded, placebo-controlled trials, presumably with minimum sources of bias, placebos are sometimes associated with improved control of symptoms such as pain and appetite but rarely with positive tumor response. Substantial improvements in symptoms and quality of life are unlikely to be due to placebo effects.

Antineoplastic Agents↗
PubMed2002

Chemotherapy with gemcitabine-containing regimens for locally recurrent or metastatic nasopharyngeal carcinoma.

BACKGROUND: Results from Phase II trials conducted in Asia have shown that gemcitabine alone (GEM) or with cisplatin (GC) is active among patients with metastatic or locally recurrent nasopharyngeal carcinoma (NPC). METHODS: At the Princess Margaret Hospital (PMH), Toronto, 32 patients with NPC were treated with GEM (n = 18) or GC (n = 14) from January 2000 to October 2001. Patients either received 1000 mg/m(2) GEM on Days 1, 8, and 15 every 28 days as a single agent, or with cisplatin (CG) given on day 2 at 70 mg/m(2). RESULTS: Most patients (91%) were of Southeast Asian ancestry and 29 (91%) had Type 2 (World Health Organization 1991 classification) nonkeratinizing histology. Sixteen of the GEM (89%) and five (36%) of the GC patients had received chemotherapy before entering the study. Median follow-up was 32 weeks (range, 2-97 weeks) for both groups. In the GEM group, there were five (28%) partial responses (PR) and one (6%) complete response (CR), giving an overall response rate of 34% (95% confidence interval [CI], 13.59). In the GC group, there were two (14%) CRs and seven PRs (50%), giving an overall response of 64% (95% CI, 35-87). Hematologic toxicity was dose limiting but uncomplicated. Nonhematologic toxicity included one patient with reversible reactivation of hepatitis, one with Grade 3 cisplatin-related sensory neuropathy, and three with cardiovascular events that were possibly related to chemotherapy. The median duration of response for the GEM and GC patients was 17 and 24 weeks and the 1-year survival rate was 48% (95% CI, 18-78) and 69% (95% CI, 40-99), respectively. Median survival has not been reached. CONCLUSIONS: Our study confirms that GEM is an active and tolerable drug for patients with NPC.

Adenocarcinoma↗
PubMed2002

Concurrent cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy and radiotherapy for breast carcinoma: a well tolerated adjuvant regimen.

BACKGROUND: The current study was conducted to assess the toxicity of concurrent adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy and radiotherapy (RT) for early breast carcinoma. METHODS: In the current study, the authors reviewed the records of 680 consecutive breast carcinoma patients who received adjuvant CMF at the Princess Margaret Hospital between 1980-1990. Surgery was comprised of mastectomy in 64% of patients, breast conservation in 35% of patients, and was unknown in 1% of patients. Two hundred two patients received concurrent CMF/RT that was defined as an overlap in CMF and RT administration of at least 21 days. Forty-seven patients received sequential CMF/RT (defined as no overlap or an overlap of < 7 days in CMF and RT administration). Other patients received CMF alone. Adverse effects of RT were graded retrospectively using the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) system. Reasons for interruption or failure to complete RT were recorded. The magnitude of chemotherapy dose reductions and delays also were noted. RESULTS: The median age of the patients was 44 years (range, 26-68 years) and 88% of the patients had lymph node-positive disease. RT was interrupted or discontinued due to side effects in 4% of patients (95% confidence interval [95% CI], 1.7-7.7%) and 0% (95% CI, 0-7.6%), respectively, of the concurrent and sequential groups (P = 0.36). The incidence of Grade 3 or Grade 4 RT toxicity was 1.5% (95% CI, 0.3-4.3%) and 2.1% (95% CI, 0.1-11.3%), respectively, for the concurrent and sequential groups (P = 0.57). The median relative dose intensity of chemotherapy for patients receiving concurrent CMF/RT, sequential CMF/RT, and CMF alone was 0.87, 0.84, and 0.85, respectively (P = 0.22). CONCLUSIONS: The results of the current study demonstrate that the concurrent administration of CMF and RT is associated with a low risk of serious toxicity and is an acceptable adjuvant regimen for patients with breast carcinoma.

Adult↗