Showing papers by "Scott M. Lippman published in 1998"
TL;DR: The results suggest the further investigation of Ad-p53 as a therapeutic agent for patients with HNSCC, and suggest that systemic or regional treatment may be tolerable.
Abstract: PURPOSEStandard therapies of head and neck squamous cell carcinoma (HNSCC) often cause profound morbidity and have not significantly improved survival over the last 30 years. Preclinical studies showed that adenoviral vector delivery of the wild-type p53 gene reduced tumor growth in mouse xenograft models. Our purpose was to ascertain the safety and therapeutic potential of adenoviral (Ad)-p53 in advanced HNSCC.PATIENTS AND METHODSPatients with incurable recurrent local or regionally metastatic HNSCC received multiple intratumoral injections of Ad-p53, either with or without tumor resection. Patients were monitored for adverse events and antiadenoviral antibodies, tumors were monitored for response and p53 expression, and body fluids were analyzed for Ad-p53.RESULTSTumors of 33 patients were injected with doses of up to 1 x 10(11) plaque-forming units (pfu). No dose-limiting toxicity or serious adverse events were noted. p53 expression was detected in tumor biopsies despite antibody responses after Ad-p53...
375 citations
181 citations
TL;DR: The data suggest that clinical and histologic assessments of the response to chemopreventive agents may be insufficient to determine their efficacy and that critical genetic alterations could be used as independent biomarkers to augment the ability to evaluate the efficacy of such agents.
Abstract: Background: The goal of chemoprevention is to reduce the risk of cancer development by reversing or blocking the tumorigenic process through the use of pharmacologic or natural agents. To determine the potential role of genetic alterations in assessing cancer risk and in evaluating the efficacy of chemopreventive agents, we studied 22 patients with advanced premalignant lesions of the head and neck who were part of a prospective cancer prevention trial that is investigating a regimen of 13-cis-retinoic acid, interferon alfa, and a-tocopherol administered for 12 months or until disease progression. Methods: We used polymerase chain reaction analysis of microsatellite DNA sequences in cells from precancerous lesions to determine the frequencies of genetic alterations—namely, loss of heterozygosity (LOH) and microsatellite instability—at chromosomal loci that are commonly deleted in head and neck cancer. Results: Prior to treatment, 17 (81%) of 21, eight (44%) of 18, and eight (42%) of 19 patients who were informative (i.e., heterozygous) at chromosomes 9p21, 3p14, and 17p13, respectively, exhibited LOH in at least one of their lesion biopsy specimens. Among nine patients who exhibited LOH at chromosome 9p21 in pretreatment biopsy specimens and who had completed at least 5 months of therapy, the genetic loss persisted in eight—including three of the four patients who exhibited complete histologic responses (i.e., no evidence of dysplasia in their biopsy specimens). Implication: Our data suggest that clinical and histologic assessments of the response to chemopreventive agents may be insufficient to determine their efficacy and that critical genetic alterations could be used as independent biomarkers to augment the ability to evaluate the efficacy of such agents. [J Natl Cancer Inst 1998;90:1545‐51]
159 citations
TL;DR: TIP had major activity in this setting, with a 58% objective response rate, 17% complete responded rate, durable complete responses (six of nine persisting), and relatively well-tolerated toxicity, with no toxic deaths.
Abstract: PURPOSETo assess the activity and toxicity profile of combined taxol (paclitaxel), ifosfamide, and platinum (cisplatin) (TIP) in patients with recurrent or metastatic squamous cell carcinoma (SCC) of the head and neck.PATIENTS AND METHODSRecurrent or metastatic head and neck SCC patients received paclitaxel 175 mg/m2 in a 3-hour infusion on day 1; ifosfamide 1,000 mg/m2 in a 2-hour infusion on days 1 through 3; mesna 600 mg/m2 on days 1 through 3; and cisplatin 60 mg/m2 on day 1, repeated every 3 to 4 weeks. All were premedicated with dexamethasone, diphenhydramine, and cimetidine. Prophylactic hematopoietic growth factors were not permitted.RESULTSFifty-two patients were assessable for response and toxicity; 53 for survival (local-regional recurrence alone in 57% and distant metastasis with or without local-regional recurrence in 43%). Overall response rate was 58% (30 of 52) of patients; complete response rate was 17% (nine of 52) of patients, with six complete responses that continued for a median 15.7...
112 citations
Journal Article•
TL;DR: An overview of issues unique to chemoprevention trials, including the use of surrogate biomarkers as end points are provided, and a discussion of the retinoids and other "classic" antioxidants are discussed.
Abstract: Cancer chemoprevention is the use of specific natural or synthetic substances with the objective of reversing, suppressing, or preventing carcinogenic progression to invasive cancer. Currently, numerous chemopreventive agents are in various stages of development and testing. Part 1 of this two-part series provides an overview of issues unique to chemoprevention trials, including the use of surrogate biomarkers as end points. This is followed by a discussion of the retinoids, such as all-trans-retinoic acid (ATRA [Vesanoid]), 9-cis-retinoic acid (9cRA), and isotretinoin (Accutane), and the carotenoids (eg, beta-carotene and lycopene) and other "classic" antioxidants (eg, vitamins E and C and selenium). Research on these agents will be delineated by disease site when applicable. Part 2, which will appear in next month’s issue, will focus on hormonally mediated chemopreventive agents, such as tamoxifen (Nolvadex), finasteride (Proscar), oral contraceptives, and dehydroepiandrosterone (DHEA). Part 2 also will cover nonantioxidant natural agents, such as calcium, the polyphenols, the isothiocyanates, and genistein; nonsteroidal anti-inflammatory drugs (NSAIDS), such as celecoxib, sulindac sulfone, and aspirin; difluro-methylornithine (DFMO [Eflornithine]); oltipraz; and N-acetylcysteine. [ONCOLOGY(11):1643-1658, 1998]
91 citations
TL;DR: The addition of infusional paclitaxel and hyperfractionated RT to FHX is feasible and the high locoregional control rate of this regimen justifies further investigation in previously untreated patients.
Abstract: PURPOSEWe have previously demonstrated high locoregional control rates in patients with poor-prognosis head and neck cancer using fluorouracil (5-FU), hydroxyurea (HU), and concomitant radiotherapy (RT) (FHX). In the trial reported here, we added paclitaxel to the FHX base and used hyperfractionated RT to determine the maximum-tolerated dose (MTD), toxicities, and response rate in a poor-prognosis group of patients.METHODSFifty-five patients who had either failed to respond to prior RT (n = 25) or surgery, had a coexistent or prior second malignancy, or who had unresectable or metastatic disease and an expected 2-year survival rate less than 10%, were treated. Chemoradiotherapy consisted of 2 Gy on days 2 to 6 (once-daily RT cohorts) or 1.5 Gy twice a day (hyperfractionated cohorts). Simultaneous HU (500 or 1,000 mg twice per day for 11 doses) and infusional 5-FU (600-800 mg/m2/d for 5 days) were given along with infusional paclitaxel at escalating doses of 5 to 25 mg/m2/d for 5 days. Granulocyte colony-s...
70 citations
Journal Article•
TL;DR: Preliminary results indicate that the TIP chemotherapy regimen produced high rates of major responses in patients with recurrent or metastatic head and neck squamous cell carcinoma, and responses were durable.
68 citations
Journal Article•
TL;DR: This second part centers on hormonally mediated chemopreventives, such as tamoxifen (Nolvadex), finasteride (Proscar), oral contraceptives, and dehydroepiandrosterone (DHEA).
Abstract: This two-part series provides an up-to-date summary of the various chemopreventive agents currently in development and testing. Part 1, published in last month’s issue, focused on the retinoids, such as all-trans-
53 citations
TL;DR: The most promising avenue of current retinoid chemoprevention in the bladder is the potent apoptosis-inducing retinoids fenretinide (4-HPR), which currently is in three phase III trials.
Abstract: Bladder cancer is strongly related to tobacco use and is estimated to cause 54,500 new cancer cases and 11,700 deaths in the United States in 1998. Approximately two thirds of new US cases will be superficial tumors, predominantly low-grade papillary. After standard therapeutic resection (with or without intravesical therapy), the superficial bladder tumor recurrence rate is 30% to 70% within 12 months of resection. Morbidity is substantial, with frequent cystoscopy, recurrence, resections, and possible cystectomy for progression to invasive cancers. Therefore, new approaches, including chemoprevention, are needed. Data suggest that bladder carcinogenesis is a multi-step, multifocal (field effect) process, possibly involving the spread of premalignant clones--all of which are prerequisites for effective chemopreventive approaches. To date, retinoids are the best-studied chemopreventive agents in this site, achieving mixed clinical results (with 13-cis-retinoic acid and etretinate) in superficial bladder tumors. This review includes the epidemiology and biology of bladder carcinogenesis in addition to preclinical and clinical retinoid data, and focuses on the most promising avenue of current retinoid chemoprevention in the bladder: the potent apoptosis-inducing retinoid fenretinide (4-HPR), which currently is in three phase III trials.
37 citations
33 citations
TL;DR: Neither regimen can be recommended for further study in patients previously treated with radiation therapy in women with recurrent cervical SCC and both regimens were generally well-tolerated and produced toxicities associated with each constituent agent's known single-agent side effects.
Journal Article•
TL;DR: It is concluded that hnRNP A2/B1 overexpression is frequently found in central airways of chronic smokers, consistent with the pattern of expression that was reported previously in airways surrounding resected primary lung cancers.
Abstract: The monoclonal antibody 703D4, which binds heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1), has been reported to detect lung cancer more than a year earlier than routine chest X-ray or cytomorphology. To explore the biological basis of this detection, we studied the expression of this antigen in the central airways of smokers with evidence of bronchial metaplasia using specimens from a previously reported, randomized retinoid chemoprevention trial. By analyzing 1078 available biopsy specimens from 147 individuals at baseline and 68 individuals who completed the intervention, we frequently detected overexpression of hnRNP A2/B1 in normal and abnormal bronchial epithelium (i.e., in 41% of normal and 37% of squamous metaplasia samples). There was no correlation between hnRNP A2/B1 overexpression and the different histological changes. In cases with hnRNP A2/B1 overexpression, immunoreactivity was homogeneously expressed in all biopsied sites. For the 68 cases with serial biopsies, there was no significant modulation of hnRNP expression by retinoid intervention or smoking status. With lung cancer cell lines, 0.5-4 microM concentrations of 13-cis-retinoic acid reduced hnRNP A2/B1 overexpression by immunocytochemistry. We conclude that hnRNP A2/B1 overexpression is frequently found in central airways of chronic smokers, consistent with the pattern of expression that we reported previously in airways surrounding resected primary lung cancers. Oral 13-cis-retinoic acid at a dose of 1 mg/kg has no demonstrable effects on modulating hnRNP A2/B1 expression in proximal bronchial epithelium.
01 Jan 1998
TL;DR: A phase I study of paclitaxel administered over 10 days, was performed to evaluate the hematologic and non-hematologic toxicities as well as to determine the maximum-tolerated dose for the 10-day infusion duration.
Abstract: Purpose: Pre-clinical data have suggested that prolonged exposure to paclitaxel enhances its cytotoxicity, but various clinical trials utilizing long-term infusions of paclitaxel have been limited by unacceptable hematologic toxicity, most notably significant neutropenia. A phase I study of paclitaxel administered over 10 days, was performed to evaluate the hematologic and non-hematologic toxicities as well as to determine the maximum-tolerated dose for the 10-day infusion duration.
TL;DR: It is suggested that chronic 13-cis-retinoic acid administration may lead to a clinically significant reduction in serum retinol levels in females, and this finding may have implications for currently ongoing chemoprevention trials that administer the drug for 3 years.