Biomedical subjects

Lillian L Siu

Publications and source records attributed to Lillian L Siu.

At least 19 recordsLinked to original sources

PubMed2026

On the Road to ROME: Defining Tissue-Liquid Concordance in Precision Oncology.

A growing body of evidence has established liquid biopsy as a promising, noninvasive platform for genomic profiling. In this commentary, we build on findings from the multicenter, randomized phase II ROME trial and interrogate the challenges and opportunities of tissue-liquid profiling concordance in improving personalized cancer treatment and survival outcomes. See related article by Botticelli et al., p. 45.

Humans↗

PubMed2007

The impact of an educational DVD on cancer patients considering participation in a phase I clinical trial.

GOALS OF WORK: The quality of informed consent in phase I trials is controversial, partially due to gaps in patient understanding. We assessed an educational DVD's impact on knowledge and satisfaction in cancer patients newly referred to a phase I clinic. MATERIALS AND METHODS: Forty-nine patients were randomly assigned to view an educational DVD (n = 22) which explained phase I trials or a placebo DVD (n = 27). Patients completed a questionnaire assessing knowledge of phase I studies and satisfaction with the DVD. The blinded interviewing physician (n = 8) rated the patient's understanding of phase I trials. MAIN RESULTS: The mean patient age was 56; 61% were male. Patients who viewed the educational DVD were less likely to believe that phase I trials determine drug efficacy (p = 0.019), more likely to know that phase I drugs have not been thoroughly studied in humans (p = 0.003), and less likely to believe that these agents have proven activity against human cancers (p = 0.008). More patients who viewed the educational DVD agreed/strongly agreed that the DVD provided useful information (p < 0.001), were confident in their knowledge of phase I trials (p = 0.031), felt aided in their decision to enter a phase I study (p = 0.011), and would have more questions for their physicians because of the DVD (p = 0.017). No statistically significant difference in physician perception of patient understanding or phase I trial accrual was observed between the educational and placebo DVD groups. CONCLUSIONS: An educational DVD increased patient knowledge and satisfaction regarding participation in phase I clinical trials.

Antineoplastic Agents↗

PubMed2006

Barriers in phase I cancer clinical trials referrals and enrollment: five-year experience at the Princess Margaret Hospital.

BACKGROUND: There is a paucity of literature on the referral outcome of patients seen in phase I trial clinics in academic oncology centres. This study aims to provide information on the accrual rate and to identify obstacles in the recruitment process. METHODS: A retrospective chart review was performed for all new patients referred and seen in the phase I clinic at the Princess Margaret Hospital between January 2000 and June 2005. Data on their demographics, medical history, and details of trial participation or non-entry were recorded. RESULTS: A total of 667 new phase I referrals were seen during the stated period. Of these patients, 197 (29.5%) patients were enrolled into a phase I trial, and 64.5% of them started trial within 1 month of the initial visit. About a quarter (165 of 667) of the patients referred were deemed ineligible at their first visit, with the most frequent reasons for ineligibility being poor performance status, unacceptable bloodwork, too many prior treatments and rapid disease progression. The remaining 305 patients (45.7%) were potentially eligible at their initial visit, but never entered a phase I trial. The main reasons for their non-entry were patient refusal, other treatment recommended first, and lack of available trials or trial spots. CONCLUSION: This study provides information on the clinical realities underlying a referral to a phase I clinic and eventual trial enrollment. Better selection of patients, appropriate education of referring physicians, and opening phase I trials with fewer restrictions on some criteria such as prior therapy may enhance their recruitment rates.

Academic Medical Centers↗

PubMed2006

Impact and perceptions of mandatory tumor biopsies for correlative studies in clinical trials of novel anticancer agents.

PURPOSE: To assess the impact and perceptions of patients, physicians, and institutional review board members (IRBs) on the issue of mandatory serial tumor biopsies to acquire tissues for correlative studies. PATIENTS AND METHODS: Complementary, self-administered questionnaires were circulated to trial patients who had previously undergone serial research-related biopsies (TPs), clinic patients who had prior diagnostic but not research-related biopsies (CPs), academic medical oncologists in Canada (MOs), and IRBs at the affiliated academic centers. RESULTS: Ten (72%) of 14 TPs, 265 (82%) of 325 CPs, 137 (66%) of 209 MOs, and 142 (49%) of 291 IRBs responded. A 5% to 10% risk of a major biopsy complication was acceptable to 22% of CPs but only to 1% of MOs or IRBs. Anxiety was reported by 30% of TPs and 45% of CPs before their biopsies. More than 82% of MOs or IRBs believed the average patient would have at least borderline anxiety before their biopsy. Among the patients, 84% would authorize their samples for additional unrelated research and 75% would agree to genetic testing. Nearly all MOs and 86% of IRBs considered it ethical to request for additional unrelated research testing. With respect to genetic testing, 82% of MOs and 72% of IRBs would request it. CONCLUSION: Although nearly all MOs and IRBs see the value in the biopsy, their threshold for acceptable risk is lower and they anticipate more associated anxiety than patients. Most patients recalled a tendency to tolerate their biopsies well with an average associated anxiety, and would allow their specimens to be tested for research purposes.

Adult↗

PubMed2006

Evaluation of adverse events experienced by older patients participating in studies of molecularly targeted agents alone or in combination.

BACKGROUND: The tolerability of molecularly targeted agents in older patients has not been specifically examined. Adverse event data from clinical trials in the Princess Margaret Hospital Phase II Consortium database were analyzed to address this question. METHODS: The Consortium database collects trial information on all patients treated with either a molecularly targeted agent alone or in combination since 2001. The frequency of adverse events was determined and analyzed by two different age groups, <65 years and >/=65 years. Toxicity indices (TI) and frequencies of dose-limiting toxicities (DLT), based on adverse events of all causalities (TI(ALL) and DLT(ALL)), and on adverse events that were at least possibly related to the molecularly targeted agent (TI(MTA) and DLT(MTA)), were calculated for both age groups. RESULTS: Four hundred and one patients who received 1,252 treatment cycles were analyzed from 19 different studies. Baseline performance status was similar between both age groups, but fewer older patients have had multiple prior regimens of chemotherapy or prior radiation therapy. A comparison of the proportions of younger and older patients experiencing DLT(ALL) and DLT(MTA) showed similar results. The TI(MTA) values were comparable between the two age groups in both single agent (3.25 versus 3.00, for <65 versus >/=65 years) and multi-agent (3.65 versus 3.00, for <65 versus >/=65 years) trials. CONCLUSIONS: Older patients seem to tolerate molecularly targeted therapies either alone or in combination with chemotherapy as well as younger patients. Age alone should not be a barrier in the administration of targeted agents.

Adult↗

PubMed2006

Understanding the attitudes of the elderly towards enrolment into cancer clinical trials.

BACKGROUND: The optimal cancer treatment for an older population is largely unknown because of the low numbers of elderly patients accrued into clinical trials. This project focuses on the attitudes of the elderly about participation in clinical trials to determine if this is one of the barriers to the involvement of this population in clinical trials. METHODS: The first phase of this study was a self-administered questionnaire mailed to 425 elderly persons with cancer, selected from Princess Margaret Hospital oncology clinics. The second phase consisted of individual semi-structured interviews with cancer patients to assess their attitudes towards cancer, its management and enrolment into cancer clinical trials. RESULTS: Ninety-four patients responded to the survey giving a response rate of 22.1%. Three quarters of respondents stated that they would be willing to participate in a clinical trial. The factors that most influenced older patients' willingness to participate in a cancer study were recommendations from a cancer doctor and the chance that the study treatment may help them feel better. Seventeen survey responders participated in interviews. Common themes from these interviews included patient-physician communication, the referral process, and the role of age in cancer care decision-making. CONCLUSION: Most elderly people, who responded to this survey, are willing to consider participation in cancer clinical trials however, elderly patients do not appear to actively seek clinical trials and few were informed of the availability of clinical trials. Physician barriers and availability of appropriate clinical trials may play a bigger role in preventing accrual of elderly cancer patients into trials.

Age Factors↗

PubMed2006

Phase I trial of sorafenib and gemcitabine in advanced solid tumors with an expanded cohort in advanced pancreatic cancer.

BACKGROUND: With its potent inhibitory effects against Raf-1 kinase and vascular endothelial growth factor receptor-2, sorafenib is a novel oral anticancer agent targeting signal transduction and angiogenic pathways. This study is designed to combine sorafenib and gemcitabine due to their compatibility in preclinical models and nonoverlapping clinical toxicities. EXPERIMENTAL DESIGN: An initial dose-escalation part of the study enrolled patients with advanced solid tumors, followed by an expanded cohort at the recommended dose for patients with advanced unresectable or metastatic pancreatic cancer. Sorafenib is administered continuously, whereas gemcitabine is given at 1,000 mg/m2 weekly x 7 followed by 1 rest week, then weekly x 3 every 4 weeks. RESULTS: Forty-two patients have been enrolled overall, including 19 in the dose-escalation part and 23 in the extended pancreatic cancer cohort. Demographics were as follows: male-to-female ratio = 26:16; median age = 61 years (range 39-83 years); Eastern Cooperative Oncology Group performance status 0:1:2 ratio = 16:21:5. The recommended dose of this combination is sorafenib 400 mg twice daily and gemcitabine 1,000 mg/m2. The most frequent grade 3 or 4 adverse events of all causalities were thrombocytopenia (28.6%), lymphopenia (21.4%), lipase elevation (19%), neutropenia (16.7%), and fatigue (14.3%). Antitumor activity was observed in both groups, with 2 (10.5%) confirmed partial responses in ovarian cancer and 12 patients (63.2%) with disease stabilization in the dose-escalation part; 13 patients (56.5%) achieved disease stabilization in the pancreatic cohort. There was no consistent pharmacokinetic drug-to-drug interaction between sorafenib and gemcitabine. CONCLUSIONS: Sorafenib and gemcitabine are well tolerated in combination; further evaluations in pancreatic and ovarian cancers are warranted.

Adult↗

PubMed2006

Natural history and chemotherapy effectiveness for advanced adenocarcinoma of the small bowel: a retrospective review of 113 cases.

BACKGROUND: Small bowel adenocarcinoma is a rare cancer that has generally been considered resistant to chemotherapy, although little has been published on the role of chemotherapy. A retrospective analysis was conducted of patients with advanced small bowel adenocarcinoma to explore chemotherapy use, and gain knowledge for ongoing management and future clinical trials. PATIENTS AND METHODS: All patients with advanced adenocarcinoma of the small bowel treated at Princess Margaret Hospital (PMH) between 1986 and 2004 were identified through the cancer registry. The medical records were reviewed for patient characteristics, treatment and outcome data. Survival statistics were estimated using the Kaplan Meier survival curves and Cox proportional regression model. RESULTS: Data on 113 patients was reviewed. Forty-four patients received palliative chemotherapy with an overall response rate (ORR) of 36% during a first or second line regimen (9% complete responses and 27% partial responses). Newer chemotherapy regimens including gemcitabine and irinotecan combinations appeared to have higher ORR, than older fluorouracil-based regimens. Some patients responded to more than one line of chemotherapy. Palliative chemotherapy predicted for overall survival (OS) in a multivariate analysis (HR 0.47, P = 0.035). CONCLUSION: Chemotherapy appears to have activity in adenocarcinoma of the small bowel. Prospective trials evaluating patient benefit are required to confirm this activity using newer systemic therapies, until such time retrospective reviews such as this will continue to guide treatment decisions.

Adenocarcinoma↗

PubMed2006

Phase I trial of gemcitabine, doxorubicin and cisplatin (GAP) in patients with advanced solid tumors.

A phase I study was conducted to determine the recommended phase II dose, safety profile and anti-tumor activity of a combination regimen of gemcitabine, doxorubicin and cisplatin (GAP). Gemcitabine (G) and doxorubicin (A) were administered on days 1 and 8 at increasing doses (starting level 800 and 15 mg/m, respectively). Cisplatin (P) was given at a fixed dose of 50 mg/m2 (day 1). Treatment cycles were repeated every 3 weeks. Nineteen patients received 76 cycles of treatment. A and G were escalated up to 20 and 1000 mg/m2, and finally de-escalated to 15 and 800 mg/m2. The dose-limiting toxicity was neutropenic fever that was observed in 21% of the patients. Non-hematological toxicities included mild/moderate nausea, vomiting, diarrhea and fatigue, observed in 58, 37, 21 and 95% of the patients, respectively. Of 19 patients with evaluable disease, six patients had a partial response yielding an overall response rate of 31.6 % (95% confidence interval 12.6-56.6%) by intention-to-treat. We conclude that GAP is an active and tolerable treatment combination, with minimal visceral organ toxicities.

Adult↗

PubMed2006

Multidisciplinary Symposium on Head and Neck Cancer. 2 December 2005, Philadelphia, PA, USA.

The Multidisciplinary Symposium on Head and Neck Cancer focused on the emerging data that underlie optimal treatment for head and neck cancers, with a particular focus on squamous cell carcinoma of the head and neck. In-depth discussions showcased the published Phase II and Phase III data on the treatment of locally advanced disease with both induction chemotherapy and concurrent chemoradiotherapy. Molecular targets of interest and relevance in this tumour type were identified, as were the agents which target these putative proteins or pathways of carcinogenesis. Preliminary results from trials incorporating molecularly-targeted agents have shown a promising role for these compounds in the management of both locally advanced and recurrent/metastatic squamous cell carcinoma of the head and neck. The Symposium brought a clear message. The management of squamous cell carcinoma of the head and neck has evolved considerably, and with the advent of newer chemotherapeutic agents and molecularly targeted therapies, this field will continue to expand over time.

Antineoplastic Agents↗

PubMed2005

Preoperative radiation with concurrent chemotherapy for resectable rectal cancer: effect of dose escalation on pathologic complete response, local recurrence-free survival, disease-free survival, and overall survival.

PURPOSE: Three Phase II studies of preoperative radiotherapy and concurrent 5FU chemotherapy were undertaken. The primary endpoints were acute toxicity and pathologic complete response rate (pCR). Secondary endpoints were local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). METHODS AND MATERIALS: A total of 134 patients with adenocarcinoma of the rectum (clinical T3/T4 or N1/N2) were treated. The initial cohort received 40 Gy in 20 fractions, the second 46 Gy in 23 fractions, and the third 50 Gy in 25 fractions. 5FU (225 mg/m2/day) was given continuously throughout radiotherapy. A total of 121 patients underwent surgical resection. RESULTS: Treatment was well tolerated. Grade 3/4 acute toxicity was observed in 13%, 4%, and 14% of patients in the 40 Gy, 46 Gy, and 50 Gy cohorts, respectively (p = 0.20). pCR was documented in 15%, 23%, and 33% of patients, respectively (p = 0.07). The 2-year actuarial LRFS was 72%, 90%, and 89% (p = 0.02); DFS was 62%, 84%, and 78% (p = 0.02); and OS was 72%, 94%, and 92%, respectively (p = 0.03). CONCLUSIONS: All treatment schedules were well tolerated. There was a trend toward increased pCR with higher doses. A statistically significant increase in LRFS, DFS, and OS was seen with radiation doses of 46 Gy and greater, but there was no difference between 46 Gy and 50 Gy.

Antimetabolites, Antineoplastic↗

PubMed2005

Comparison of outcomes of phase II studies and subsequent randomized control studies using identical chemotherapeutic regimens.

PURPOSE: To determine whether promising results from phase II studies could be reproduced in phase III studies, and to examine which characteristics of phase II studies might be of predictive value for subsequent phase III studies. METHODS: We searched for all phase III studies of chemotherapy in advanced solid malignancies, published in the English language literature from July 1998 to June 2003. Each phase III study was reviewed to identify preceding phase II studies. Phase II and phase III studies included in this analysis must have used identical regimens. Data were extracted from both phase II and phase III studies. RESULTS: Of 181 phase III studies identified, 43 used therapeutic regimens identical to those in 49 preceding phase II studies. Twelve phase III studies (28%) were "positive." The vast majority (81%) of phase III studies have lower response rates than preceding phase II studies, with a mean difference of 12.9% among all studies analyzed. None of the phase II study characteristics evaluated significantly predicted for "positive" phase III studies, but the sample size of phase II studies demonstrated a trend toward being predictive (P = .083). CONCLUSION: Promising results from phase II studies frequently do not translate into "positive" phase III studies. Response rates in most phase III studies are lower than those in preceding phase II studies.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Analysis of treatment practices for elderly cancer patients in Ontario, Canada.

PURPOSE: Older patients are underrepresented in many areas of cancer services utilization and in clinical trial enrollment. This study evaluates whether age, when adjusted for sex, comorbidity, stage, tumor site, geography, and time period, is predictive of cancer treatment practice. METHODS: First, we used the Ontario Cancer Registry (OCR) to examine for any apparent differences in treatment practices between elderly (> or = 70 years) and younger patients in the last three decades. Second, we performed a chart review of 1,505 patients with lung, breast, and colorectal cancers seen in Ontario either at an urban center, the Princess Margaret Hospital, or at a rural center, the Northwestern Regional Cancer Centre. Patients were randomly selected from two time periods, 1977 to 1978 and 1997; and the study population was to comprise at least 50% elderly patients. RESULTS: OCR data demonstrated that, in some settings, such as colorectal cancer, the proportions of elderly cancer patients who were referred to cancer centers and who received any cancer treatment were lower than their younger counterparts. The chart review data showed that increasing age was a significant negative predictor for receiving any cancer treatment (P < .001, multivariate analysis) and for having a clinical trial discussion with the treating specialist (P < .001, multivariate analysis). CONCLUSION: Independent of other factors, older age is consistently a cause of disparity in cancer treatment practice and in clinical trial discussion with patients. By increasing the accrual rate of elderly cancer patients in clinical trials, a better understanding of appropriate therapies for this patient population can be obtained and may, thereby, impact on their cancer-related morbidity and mortality.

Age Distribution↗

PubMed2005

Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials.

PURPOSE: Older patients are significantly underrepresented in cancer clinical trials. A literature review was undertaken to identify the barriers that impede the accrual of this vulnerable population onto clinical trials and to determine what specific strategies are needed to improve the representation of older patients in research studies. METHODS: A systematic literature search was undertaken using several different strategies to identify relevant articles. RESULTS: Nine of 31 relevant papers from 159 citations were included. Age is a significant barrier to recruitment; only a quarter to one third of potentially eligible older patients are enrolled onto trials. Physicians' perceptions, protocol eligibility criteria with restrictions on comorbid conditions, and functional status to optimize treatment tolerability are the most important reasons resulting in the exclusion of older patients. Other barriers include the lack of social support and the need for extra time and resources to enroll these patients. Conversely, older patients do not view their age as an important reason for refusing trials. CONCLUSION: Specific clinical trials confined to older patients should be conducted to evaluate tumor biology, treatment tolerability, and the effect of comorbid conditions. Protocol designs need to stratify for age and be less restrictive with respect to exclusions on functional status, comorbidity, and previous cancers, such that results are generalizable to older patients. Physician education to dispel unfounded perceptions, improved access to available clinical trials, and provision of personnel and resources to accommodate the unique requirements of an older population are possible solutions to remove the barriers of ageism.

Age Factors↗

PubMed2005

Phase I study of the multidrug resistance inhibitor zosuquidar administered in combination with vinorelbine in patients with advanced solid tumours.

BACKGROUND: Zosuquidar (LY335979) is an oral P-glycoprotein modulator. This phase I study was designed to determine the maximum tolerated dose (MTD) of zosuquidar in combination with vinorelbine. The effects of zosuquidar on vinorelbine pharmacokinetics were also examined. DESIGN: Patients with advanced solid tumours were treated with escalating doses of zosuquidar administered every 8-12 h on days 7-9 and 14-16 during cycle 1 then days 0-2, 7-9, and 14-16 from cycle 2 onwards, with vinorelbine 22.5-30 mg/m2 IV on days 1, 8 and 15 every 28 days. RESULTS: Of 21 patients registered, 19 were treated at four dose levels (zosuquidar 100-300 mg/m2). Two patients had prolonged and febrile neutropenia at the second dose level resulting in a reduction of the dose of vinorelbine in subsequent dose levels. There was another patient with dose-limiting febrile neutropenia at dose level four which resulted in the expansion of the dose level three. Eight patients had stable disease and no objective responses were seen. Vinorelbine pharmacokinetic studies showed reduced clearance when given with zosuquidar. CONCLUSIONS: The MTD was zosuquidar 300 mg/m2 orally every 12 h for 3 days weekly for 3 weeks with vinorelbine 22.5 mg/m2 IV weekly for 3 weeks every 28 days. Zosuquidar may inhibit vinorelbine clearance to a modest degree.

Administration, Oral↗

PubMed2005

Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial.

PURPOSE: Biliary cancer has a poor prognosis, and chemotherapy has had little impact. The objectives of this trial were to determine the response rate, time to disease progression, survival, and safety profile of the combination of gemcitabine and capecitabine (GemCap) in patients with advanced biliary cancer. PATIENTS AND METHODS: Eligible patients had pathologically proven, locally advanced or metastatic adenocarcinoma arising from the intra- and extrahepatic bile ducts or gallbladder with no prior chemotherapy. Patients were treated on a 3-week cycle consisting of capecitabine at 650 mg/m(2) orally twice a day for 14 days and gemcitabine at a fixed dose of 1,000 mg/m(2) intravenously over 30 minutes on days 1 and 8. RESULTS: Forty-five patients were enrolled between July 2001 and January 2004. Fifty-three percent of patients had cholangiocarcinoma, 47% had gallbladder cancer, and 89% had metastatic disease. The overall objective response rate was 31%, with an additional 42% of patients with stable disease, for a disease control rate of 73%. The median overall survival time was 14 months (95% CI, 7.3 months to not available), and the median progression-free survival time was 7 months (95% CI, 4.6 to 11.8 months). This chemotherapy combination was generally well tolerated. Transient neutropenia, thrombocytopenia, fatigue, and hand-foot syndrome were commonly observed but were easily managed without discontinuing further treatment. CONCLUSION: The significant antitumor activity combined with a mild toxicity profile seen in this study argue that GemCap chemotherapy may benefit patients with advanced biliary cancer. This regimen warrants further evaluation in a randomized study with survival and quality of life end points.

Adenocarcinoma↗

PubMed2005

A Phase I trial of prolonged administration of lovastatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or of the cervix.

Squamous cell carcinomas of the head and neck (HNSCC) and of the cervix (CC) are particularly sensitive to the apoptotic effects of lovastatin in vitro. In this Phase I study, the safety and maximum related dose (MTD) of lovastatin was evaluated in these specific clinical settings. This was a Phase I open-label study to determine the recommended Phase II dose (RPTD) of lovastatin in advanced HNSCC or CC. This study involved a dose and duration escalation of lovastatin starting at 5/mg/kg/day x 2 weeks, every 21 days, until the MTD was reached. Plasma samples were collected for pharmacokinetic analysis. All 26 patients enrolled were evaluable. Dose-limiting toxicity (DLT) consisting of reversible muscle toxicity was seen at 10 mg/kg/day x 14 days. Toxicity may be related to relative renal insufficiency. The MTD was determined to be 7.5 mg/kg/day x 21 days, every 28 days. The low lipid levels experienced on study did not translate into adverse events. Biologically relevant plasma lovastatin levels were obtained. No objective responses were seen but the median survival of patients on study was 7.5 months (mean 9.2 +/- 1.5 months). Stable disease (SD) for more than 3 months was seen in 23% of patients. One patient achieved SD and clinical benefit for 14 months on study and a further 23 months off treatment. The disease stabilisation rate of 23% seen in these end-stage patients is encouraging. We conclude that the administration of lovastatin at 7.5 mg/kg/day for 21 consecutive days on a 28-day schedule is well tolerated in patients with good renal function and warrants further clinical evaluation.

Adult↗

PubMed2005

Imatinib mesylate in patients with adenoid cystic cancers of the salivary glands expressing c-kit: a Princess Margaret Hospital phase II consortium study.

PURPOSE: This study aimed to assess the antitumor activity of imatinib in adenoid cystic carcinoma (ACC) of the salivary gland expressing c-kit. A high level of c-kit expression has been identified in more than 90% of ACCs. Imatinib specifically inhibits autophosphorylation of the bcr-abl, platelet-derived growth factor receptor beta, and c-kit tyrosine kinases. PATIENTS AND METHODS: In a single-arm, two-stage, phase II clinical trial, adult patients with unresectable or metastatic ACC measurable by Response Evaluation Criteria in Solid Tumors Group criteria and expressing c-kit by immunohistochemistry were treated with imatinib 400 mg orally bid. Response was assessed every 8 weeks. RESULTS: Sixteen patients have been enrolled onto the study; 10 were female. Median age was 47 years (range, 31 to 69 years). Median Eastern Cooperative Oncology Group performance status was 1 (range, 0 to 2). Fourteen patients had lung metastases, 14 had prior radiotherapy, and six had prior chemotherapy. Toxicities occurring in at least 50% of patients included fatigue, nausea, vomiting, diarrhea, anorexia, edema, dyspnea, and/or headache, usually of mild to moderate severity. In 15 patients assessable for response, no objective responses have been observed. Nine patients had stable disease as best response. Six patients had progressive disease after two cycles. CONCLUSION: Because of the lack of activity, the study has been stopped after the first stage and additional evaluation of imatinib in this population is not warranted. Overexpression of wild-type c-kit was not sufficient for clinical benefit from imatinib in ACC. Accrual to this study was rapid for a relatively rare cancer, encouraging additional efforts to identify more effective systemic therapy for these patients.

Administration, Oral↗