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Daniel Sargent

Publications and source records attributed to Daniel Sargent.

8 recordsLinked to original sources
PubMed2006

Current issues in adjuvant treatment of stage II colon cancer.

BACKGROUND: Adjuvant chemotherapy with 5-fluorouracil modulated by folinic acid, combined with oxaliplatin, has now become an accepted standard of care for patients with stage III colon cancer. In contrast, the use of adjuvant therapy for stage II patients remains controversial, and the identification of reliable prognostic factors to aid therapeutic decision making is crucial. METHODS: The authors critically review the results of clinical trials and meta-analyses investigating the value of adjuvant chemotherapy for stage II patients, emphasizing the heterogeneous nature of this population and the difficulty of performing clinical trials with sufficient power to reliably assess treatment efficacy. They also discuss the evidence concerning potential prognostic factors, particularly molecular markers. RESULTS: Available clinical trial data do not support the routine use of adjuvant chemotherapy for all stage II patients but suggest that it should be considered, particularly for certain high-risk patients. Recent guidelines advocate considering factors such as tumor differentiation, tumor perforation, number of lymph nodes examined, and T stage when assessing the likely benefit:risk ratio. Microsatellite instability and allelic imbalance seem to be strong predictors of good and poor prognosis, respectively, and in the near future, therapeutic decision-making models are likely to be further refined by the inclusion of such molecular markers. CONCLUSIONS: There is growing evidence that the prognosis of certain stage II patients with unfavorable prognostic factors can be improved by adjuvant chemotherapy, and increasingly refined tools are now available to define those most likely to benefit. Referral of stage II patients for individual assessment is strongly recommended.

Allelic Imbalance↗
PubMed2006

End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival?

The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed.

Breast Neoplasms↗
PubMed2006

General and statistical hierarchy of appropriate biologic endpoints.

The introduction of newer classes of chemotherapeutic agents, with varying mechanisms of action by which they affect tumor growth and viability, has challenged the traditional norms of clinical trial design and drug approval in oncology. Most notably, the emergence of cytostatic biologic agents with antitumor efficacy has necessitated reassessment of appropriate primary endpoints for phase II and III trials in advanced disease from both a clinical and regulatory standpoint. Recent data in the field establishes an endpoint hierarchy, which places progression-free survival (PFS) between overall survival (OS) and response rate (RR) as appropriate primary endpoints for assessing the clinical efficacy of cytostatic and cytotoxic agents.

Antineoplastic Agents↗
PubMed2004

Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment.

PURPOSE: Fluorouracil (FU)-leucovorin (LV), irinotecan, and oxaliplatin administered alone or in combination have proven effective in the treatment of advanced colorectal cancer (CRC). Combination protocols using FU-LV with either irinotecan or oxaliplatin are currently regarded as standard first-line therapies in this disease. However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated. MATERIALS AND METHODS: We analyzed data from seven recently published phase III trials in advanced CRC to correlate the percentage of patients receiving second-line therapy and the percentage of patients receiving all three agents with the reported median OS, using a weighted analysis. RESULTS: The reported median OS is significantly correlated with the percentage of patients who received all three drugs in the course of their disease (P =.0008) but not with the percentage of patients who received any second-line therapy (P =.19). In addition, the use of combination protocols as first-line therapy was associated with a significant improvement in median survival of 3.5 months (95% CI, 1.27 to 5.73 months; P =.0083). CONCLUSION: Our results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Short-term quality-of-life outcomes following laparoscopic-assisted colectomy vs open colectomy for colon cancer: a randomized trial.

CONTEXT: Laparoscopic-assisted colectomy (LAC) has emerged as the preferred minimally invasive surgical strategy for diseases of the colon. The safety and efficacy of LAC for colon cancer are unknown, and the nature and magnitude of any quality-of-life (QOL) benefit resulting from LAC for colon cancer is also unknown. OBJECTIVE: To compare short-term QOL outcomes after LAC vs open colectomy for colon cancer. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized controlled trial (Clinical Outcomes of Surgical Therapy [COST]). Between September 1994 and February 1999, 37 of 48 centers provided data for the QOL component of the trial for 449 consecutive patients with clinically resectable colon cancer. MAIN OUTCOME MEASURES: Scores on the Symptoms Distress Scale (SDS), Quality of Life Index, and a single-item global rating scale at 2 days, 2 weeks, and 2 months postoperative; duration of postoperative in-hospital analgesic use; and length of stay. RESULTS: Of 449 patients, 428 provided QOL data. In an intention-to-treat analysis comparing SDS pain intensity, SDS summary, QOL Index summary, and global rating scale scores at each time point, the only statistically significant difference observed between groups was the global rating scale score for 2 weeks postsurgery. The mean (median) global rating scale scores for 2 weeks postsurgery were 76.9 (80) for LAC vs 74.4 (75) for open colectomy (P =.009). While in the hospital, patients assigned to LAC required fewer days of both parenteral analgesics compared with patients assigned to open colectomy (mean [median], 3.2 [3] vs 4.0 [4] days; P<.001) and oral analgesics (mean [median], 1.9 [1] vs 2.2 [2] days; P =.03). CONCLUSION: Only minimal short-term QOL benefits were found with LAC for colon cancer compared with standard open colectomy. Until ongoing trials establish that LAC is as effective as open colectomy in preventing recurrence and death from colon cancer, this procedure should not be offered to patients with colon cancer.

Adult↗
PubMed2002

Issues in clinical trial design for tumor marker studies.

Scientific inquiry into the discovery, development, and application of tumor markers is proceeding rapidly. Despite this explosion in research and interest, the design of studies to formally assess the value of tumor markers in clinical practice is inconsistent and immature. Indeed, few markers have been widely accepted into standard clinical practice. Many issues must be prospectively considered in a methodical, systematic, and scientific fashion if progress is to be made in the development of validated tests that will have value in the management of patients with cancer. The purpose of this report is to present a discussion of the issues involved in designing clinical studies of putative tumor markers which provide sufficient data to result in the incorporation of the marker into clinical practice. We will focus on the design of studies to demonstrate and validate the clinical utility of both prognostic and predictive markers. Topics to be covered include issues of patient and sample heterogeneity, the prevalence of the marker, the sample capture rate, and the choice of endpoints. This will be followed by explicit consideration of study design, specifically the trial randomization schema for both prognostic and predictive factor studies.

Biomarkers, Tumor↗