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Neal J Meropol

Publications and source records attributed to Neal J Meropol.

50 records · Page 3Linked to original sources
PubMed2003

Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: analysis of histopathology and outcome.

To examine the histopathologic effect of neoadjuvant therapy and its impact on survival in patients with carcinoma of the pancreas, we retrospectively reviewed the records of 116 patients who underwent resections for pancreatic cancer from 1987 to 2000. Median follow-up of surviving patients was 19 mo(range 4-150 mo). Preoperative chemotherapy was administered in 61 patients (53%) and consisted of 5-fluorouracil/mitomycin C in 35 patients and gemcitabine in 26 patients, given concurrently with external beam radiation (5040 cGy). All resections were performed with curative intent (98 Whipples, 11 total, 6 distal, and 1 central pancreatectomy). Histopathologic examination included an estimation of the amount of fibrosis present in the tumor specimen (expressed as the percentage of fibrosis identified relative to the amount of neoplastic cells present). The mean fibrosis level for the series was 56% (range 5% to 100%). The administration of neoadjuvant therapy resulted in greater fibrosis (73%) than no preoperative treatment (38%) (p = 0.0001). Higher mean fibrosis levels were observed in patients with negative lymph nodes (p = 0.0006) and negative margins (p = 0.05). Factors associated with improved survival(log rank test) included: negative margins (p = 0.001), negative lymph nodes (p = 0.03), and use of neoadjuvant therapy (p = 0.03). Median survival in the neoadjuvant group was 23 mo vs 16 mo without preoperative therapy (p = 0.03). In conclusion, the use of neoadjuvant therapy resulted in a greater degree of fibrosis in the specimen. Patients with negative margins and negative lymph nodes had a greater amount of fibrosis present, and these were significant predictors of improved outcome. Although retrospective,this series suggests an improvement in survival in patients treated with neoadjuvant therapy.

Adenocarcinoma↗
PubMed2003

Development of new agents for the treatment of advanced colorectal cancer.

During the past decade, there have been several significant advances in the treatment of metastatic colorectal cancer. These include the introduction of the cytotoxic agents capecitabine, irinotecan, and oxaliplatin. Given their diverse mechanisms of action and toxicity profiles, combinations of fluoropyrimidines, irinotecan, and oxaliplatin have proven feasible and have improved patient outcomes compared with 5-fluorouracil alone. Recently, improved understanding of the biology of colorectal cancer has led to the identification of new molecular targets and the development of pharmacologic agents that hold promise for greater tumor selectivity than traditional cytotoxic agents. Two approaches with early indications of clinical activity against colorectal cancer are inhibition of epidermal growth factor receptor signaling and inhibition of the vascular endothelial growth factor pathway. Furthermore, biochemical and genetic profiling of individual tumors, as well as patient genotyping, may ultimately guide clinicians in making rational treatment decisions based on predicted antitumor efficacy or toxicity of selected agents. This article reviews these recent advances in the systemic treatment of colorectal cancer, including discussion of promising agents in clinical development.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Sequelae of axillary lymph node dissection in older women with stage 1 and 2 breast carcinoma.

BACKGROUND: There are few data on the long-term sequelae of axillary dissection among older breast carcinoma patients. We describe the impact of axillary dissection in a cohort of older women. METHODS: A longitudinal cohort of 571 patients with Stage 1 and 2 breast carcinoma, 67 years and older, diagnosed between 1995 and 1997 from 29 hospitals in five regions, and followed for 2 years. Data were collected from patients and medical charts. The primary outcome was posttreatment quality of life. Generalized estimation equation longitudinal modeling was used to evaluate the outcome, controlling for baseline function, comorbidity, age, clinical status, and other factors. RESULTS: Sixty percent of women reported arm problems at some time in the 2 years after surgery. The cumulative risk of having arm problems 2 years posttreatment was three times higher (95% confidence interval 1.94-4.67) for women who underwent axillary surgery compared with women without axillary surgery, controlling for covariates. The effects of having axillary dissection and arthritis were multiplicative 2 years postsurgery. Arm problems were, in turn, the primary determinate of lower physical and mental functioning (P = 0.0001 and 0.04, respectively), controlling for other factors. Undergoing axillary dissection did not lessen fears about recurrence. CONCLUSIONS: Arm problems after axillary dissection have a consistent negative impact on quality of life, suggesting that the risks may outweigh the potential benefits in this population.

Aged↗
PubMed2002

Phase I and pharmacokinetic study of irinotecan in combination with raltitrexed.

PURPOSE: To determine the maximum tolerated dose (MTD) of raltitrexed when given with irinotecan and to evaluate the pharmacokinetics of these two agents when given in combination. METHODS: Patients with advanced solid tumors received irinotecan intravenously over 90 min on days 1 and 8 of each 21-day cycle, with raltitrexed given intravenously over 15 min after irinotecan either on day 1 (cohorts 1-7) or day 2 (cohorts 8-9). The 39 patients received irinotecan and raltitrexed in cohorts of three to six patients at the following dose levels (mg/m(2)): 100/1.0, 100/1.5, 100/2.0, 100/2.5, 100/3.0, 100/3.5, 125/3.0, 75/3.0, 100/3.0. Pharmacologic monitoring of irinotecan and raltitrexed was carried out during cycle 1. RESULTS: A total of 39 patients received irinotecan and raltitrexed in cohorts of three to six patients at nine dose levels. The MTD with dosing of irinotecan on days 1 and 8 and raltitrexed on day 1 was 100 mg/m(2) and 3.0 mg/m(2), respectively, every 21 days, with dose-limiting toxicities (DLTs) of fatigue, neutropenia and diarrhea. When raltitrexed was administered 24 h after irinotecan, these doses exceeded the MTD. No pharmacologic interactions were observed between these agents, and no correlations between pharmacokinetic parameters and toxicity were noted. Of 26 patients with colorectal cancer, 6 had objective partial responses (23%). Four of these patients had previously received a 5-FU-based regimen, two for metastatic disease. CONCLUSIONS: Irinotecan can be safely administered with raltitrexed on a day-1 and day-8 schedule at 100 mg/m(2) and 3.0 mg/m(2), respectively, every 21 days. When raltitrexed was given on day 2, these doses were not tolerated, necessitating a dose reduction of the irinotecan to 75 mg/m(2). This regimen possesses clinical activity in patients with colorectal cancer.

Adult↗
PubMed2002

Patient and provider characteristics that affect the use of axillary dissection in older women with stage I-II breast carcinoma.

BACKGROUND: Axillary dissection for the evaluation and treatment of patients with breast carcinoma often is not performed in older women. The objective of this study was to examine patient, clinical, and surgeon characteristics associated with the use of axillary dissection after breast-conserving surgery (BCS). METHODS: A cohort of 464 women age > or = 67 years who were newly diagnosed with Stage I-II breast carcinoma and who underwent BCS were surveyed along with their 158 surgeons, and their medical records were reviewed. Patient, tumor, and provider characteristics were examined for association with the omission of axillary dissection. RESULTS: The majority of women (63.4%) underwent axillary lymph node dissection after BCS. Increasing age was associated strongly with decreasing odds of undergoing axillary lymph node dissection, even after considering patient health and preferences, clinical factors, and provider factors (odds ratio [OR], 0.11; 95% confidence interval [95%CI], 0.05-0.27). Independent of age and other factors, women in the lowest quartile of physical functioning were 37% less likely to undergo axillary lymph node dissection compared with women in the highest quartile (OR, 0.63; 95%CI, 0.62-0.64). Patients who were cared for by surgeons with subspecialty training in oncology were 60% less likely to undergo axillary lymph node dissection compared with patients who were cared for by other surgeons, even after considering other factors (OR, 0.41; 95%CI, 0.25-0.68). CONCLUSIONS: The results of this study demonstrated a correlation between lower use of axillary dissection and advancing age, lower functional status, and greater surgeon training. These findings suggest that simple, age-based considerations are important but are not the sole determinants of variations in treatment.

Age Factors↗
PubMed2002

Phase I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers.

PURPOSE: PV701, a replication-competent strain of Newcastle disease virus, causes regression of tumor xenografts after intravenous administration. This phase I study was designed to define the maximum-tolerated dose (MTD) and safety of single and multiple intravenous doses of PV701 as a single agent in patients with cancer. PATIENTS AND METHODS: Seventy-nine patients with advanced solid cancers that were unresponsive to standard therapy were enrolled. Four PV701 intravenous dosing regimens were evaluated: (1) single dose: one dose every 28 days; (2) repeat dose: three doses in 1 week every 28 days; (3) desensitizing: one lower dose followed by two higher doses in 1 week every 28 days; and (4) two week: one lower dose followed by five higher doses over 2 weeks every 21 days. RESULTS: A 100-fold dose intensification was achieved over 195 cycles. A first-dose MTD of 12 x 10(9) plaque-forming units (PFU)/m(2) was established for outpatient dosing. After an initial dose of 12 x 10(9) PFU/m(2), patients tolerated an MTD for subsequent doses of 120 x 10(9) PFU/m(2). The most common adverse events were flu-like symptoms that occurred principally after the first dose and were decreased in number and severity with each subsequent dose. Tumor site-specific adverse events and acute dosing reactions were also observed but not cumulative toxicity. Objective responses occurred at higher dose levels, and progression-free survival ranged from 4 to 31 months. Tumor tissue from one patient was obtained after 11 months of therapy and showed evidence of PV701 particles budding from the tumor cell membrane by electron microscopy and a pronounced lymphoplasmacytic infiltrate by histologic examination. CONCLUSION: PV701 warrants further study as a novel therapeutic agent for cancer patients.

Adult↗
PubMed2002

Communication between physicians and older women with localized breast cancer: implications for treatment and patient satisfaction.

PURPOSE: To identify factors associated with patient-physician communication and to examine the impact of communication on patients' perception of having a treatment choice, actual treatment received, and satisfaction with care among older breast cancer patients. MATERIALS AND METHODS: Data were collected from 613 pairs of surgeons and their older (greater-than-or-equal 67 years) patients diagnosed with localized breast cancer. Measures of patients' self-reported communication included physician- and patient-initiated communication and the number of treatment options discussed. Logistic regression analyses were conducted to examine the relationships between communication and outcomes. RESULTS: Patients who reported that their surgeons mentioned more treatment options were 2.21 times (95% confidence interval [CI], 1.62 to 3.01) more likely to report being given a treatment choice, and 1.33 times (95% CI, 1.02 to 1.73) more likely to get breast-conserving surgery with radiation than other types of treatment. Surgeons who were trained in surgical oncology, or who treated a high volume of breast cancer patients (greater-than-or-equal 75% of practice), were more likely to initiate communication with patients (odds ratio [OR] = 1.62; 95% CI, 1.02 to 2.56; and OR = 1.68; 95% CI, 1.01 to 2.76, respectively). A high degree of physician-initiated communication, in turn, was associated with patients' perception of having a treatment choice (OR = 2.46; 95% CI, 1.29 to 4.70), and satisfaction with breast cancer care (OR = 2.13; 95% CI, 1.17 to 3.85) in the 3 to 6 months after surgery. CONCLUSION: Greater patient-physician communication was associated with a sense of choice, actual treatment, and satisfaction with care. Technical information and caring components of communication impacted outcomes differently. Thus, the quality of cancer care for older breast cancer patients may be improved through interventions that improve communication within the physician-patient dyad.

Age Factors↗
PubMed2002

Drug development in pancreatic cancer: finally, biology begets therapy.

Pancreatic cancer is rarely curable, and only 5% of patients achieve long-term survival. The vast majority of patients present with metastatic or unresectable disease. Standard chemotherapy with gemcitabine provides clinical benefit to only a small minority of patients. Thus, the development and investigation of new therapies is clearly needed. As knowledge of the underlying biology of pancreatic cancer has increased, targeted therapies based upon preclinical laboratory work have been developed, and are entering clinical trials. Some of these agents lack traditional dose-limiting toxicities (DLTs) at biologically active doses, and therefore clinical evaluation may not follow traditional guidelines for cytotoxic drug development. This article focuses on targeted therapies currently undergoing clinical evaluation in pancreatic cancer. Classes of therapeutics reviewed include those targeting tumor-microenvironment interactions (matrix metalloproteinase inhibitors, vascular endothelial growth-factor blockade), signal transduction (e.g., farnesyltransferase inhibitors), growth-factor receptors (epidermal growth-factor receptor blockade, Her-2/neu, gastrin), and vaccine approaches. Currently, there is a renewed optimism that the clinical application of biologic understanding will lead to an improved outcome for patients with pancreatic cancer.

Antineoplastic Agents↗
PubMed2002

Correlates of colorectal cancer screening compliance and stage of adoption among siblings of individuals with early onset colorectal cancer.

Concepts from the health belief, transtheoretical, and dual process models were used to examine how siblings of individuals diagnosed with colorectal cancer (CRC) before age 56 made decisions about CRC screening. Siblings (N = 504) were assessed for CRC screening practices and intentions, pros, cons, processes-of-change, perceived risk of CRC, perceived severity of CRC, preventability of CRC, cancer-related distress, and sibling relationship closeness. Physician and family recommendation and knowledge were also assessed. Fifty-seven percent of participants (n = 287) were compliant with CRC screening. Logistic regression indicated that perceived pros and cons, perceived risk, commitment to screening, health care avoidance, and sibling closeness were associated with screening compliance. Physician and family recommendation were also strong correlates. A similar set of factors was associated with stage of adoption of CRC screening.

Adoption↗
PubMed2002

Preoperative chemoradiation in the management of adenocarcinoma of the body of the pancreas.

Adenocarcinoma of the body of the pancreas has been traditionally associated with low resectability and poor prognosis. We reviewed 30 consecutive cases of pancreatic body adenocarcinoma presenting between 1988 and 2001. Twenty-six (87%) patients received preoperative chemotherapy (either 5-fluorouracil with or without mitomycin C or gemcitabine) plus radiation therapy (50.4 Gy), and four patients received chemoradiation postoperatively. During or shortly after chemoradiation 16 (53%) patients developed distant metastasis (n = 12), tumor progression (n = 2), or fatal septic complications (n = 2). Fourteen patients underwent surgical resection with curative intent. Resections performed included distal subtotal pancreatectomies (n = 6), extended pancreaticoduodenectomies (n = 6), and total pancreatectomies (n = 2). Ten patients (71%) required vascular reconstruction as a result of involvement of the portal vein or the superior mesenteric, hepatic arterial, or celiac vessels. Median overall survival was 34 months (range 8-152) for the resected group as compared with 8 months (range 1-14) in the unresected group (P = 0.005). Five-year actuarial overall survival is projected at 45 per cent for the resected group. In this poor-prognostic subset of patients with pancreatic cancer preoperative chemoradiation followed by an aggressive surgical approach was associated with resectability and long-term survival of a significant minority of patients.

Adenocarcinoma↗
PubMed2002

Phase I and pharmacokinetic study of once daily oral administration of S-1 in patients with advanced cancer.

PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicities(DLTs), and pharmacokinetics of S-1, a combination of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), and oxonic acid, administered once daily in patients with advanced cancer. EXPERIMENTAL DESIGN: Eighteen patients with refractory malignancies were treated with S-1 administered once daily for 21 consecutive days, followed by a 1-week break. Of 16 evaluable patients, 6 were treated at a dose of 50 mg/m(2)/day, and 10 were treated at 60 mg/m(2)/day. RESULTS: DLTs were observed in 1 of 6 evaluable patients treated with 50 mg/m(2)/day and in 4 of 10 evaluable patients treated with 60 mg/m(2)/day. DLTs included diarrhea, nausea/vomiting, fatigue, and hyperbilirubinemia. The maximum tolerated dose was 50 mg/m(2)/day. Pharmacokinetic data are consistent with potent modulation of 5-fluorouracil (5-FU) by CDHP, with prolonged half-life and 5-FU AUC at least 10-fold higher than reported in previous studies of equitoxic doses of tegafur modulated by uracil. Pharmacodynamic analysis demonstrated a correlation between diarrhea grade and both 5-FU C(max) (r = 0.57, P < 0.05) and 5-FU area under the curve (r = 0.74, P < 0.01). CONCLUSIONS: The recommended Phase II dose of S-1 administered once daily for 21 consecutive days of 28 is 50 mg/m(2). The pharmacokinetic data presented provide evidence of 5-FU modulation by CDHP. Pharmacodynamic analyses suggest that the utility of pharmacology-based dosing of S-1 should be explored in future trials. Evaluation of once-daily dosing of S-1 in malignancies for which fluoropyrimidines have known antitumor activity is warranted.

Administration, Oral↗
PubMed2002

A phase I trial of escalating doses of trastuzumab combined with daily subcutaneous interleukin 2: report of cancer and leukemia group B 9661.

PURPOSE: The purpose of this study was to determine the toxicity of escalating doses of trastuzumab when combined with a fixed dose regimen of interleukin (IL)-2. EXPERIMENTAL DESIGN: Eligible patients had nonhematological malignancies for which standard therapy did not exist or was no longer effective and had tumors that overexpressed HER2. IL-2 was initially administered at a dose of 1.25 million IU/m(2) (low dose) s.c. daily except for 3 days every 2 weeks, when it was given at a dose of 15 million IU/m(2) (intermediate dose). These doses were reduced to 1.0 million and 12 million IU/m(2) after the first 18 patients. Trastuzumab was administered i.v. just before the first intermediate IL-2 dose and was escalated in cohorts of six or more patients from 1 mg/kg every 2 weeks to 8 mg/kg weekly. In vitro cytotoxicity testing was performed with patient peripheral blood mononuclear cells and HER2-overexpressing cell lines. RESULTS: Forty-five patients were treated. Dose-related toxicity from trastuzumab was not observed. IL-2-related toxicities such as fever, chills, and fatigue were less common with the reduced doses of IL-2. There were two grade 3 and three grade 4 pulmonary reactions. Four major responses were observed, all in breast cancer patients treated with trastuzumab doses of at least 4.0 mg/kg. Although IL-2 produced expansion of natural killer cell subsets, there was no correlation between in vitro cytotoxicity and clinical response. CONCLUSIONS: A regimen of IL-2 combined with trastuzumab is feasible, and response numbers are encouraging. Further testing of this regimen is warranted if the pulmonary toxicity can be ameliorated.

Adult↗
PubMedDate not supplied

An exploration of relative health stock in advanced cancer patients.

OBJECTIVE: The authors sought to empirically test whether relative health stock, a measure of patients' sense of loss in their health due to illness, influences the treatment decisions of patients facing life-threatening conditions. Specifically, they estimated the effect of relative health stock on advanced cancer patients' decisions to participate in phase I clinical trials. METHOD: A multicenter study was conducted to survey 328 advanced cancer patients who were offered the opportunity to participate in phase I trials. The authors asked patients to estimate the probabilities of therapeutic benefits and toxicity, their relative health stock, risk preference, and the importance of quality of life. RESULTS: Controlling for health-related quality of life, an increase in relative health stock by 10 percentage points reduced the odds of choosing to participate in a phase I trial by 16% (odds ratio = 0.84, 95% confidence interval = 0.72, 0.97). CONCLUSION: Relative health stock affects advanced cancer patients' treatment decisions.

Clinical Trials, Phase I as Topic↗