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1.
J Geriatr Oncol ; 8(1): 18-22, 2017 01.
Article in English | MEDLINE | ID: mdl-27491498

ABSTRACT

OBJECTIVE: Platinum-based doublet chemotherapy is the standard for most patients with advanced non-small cell lung cancer (NSCLC). Toxicity concerns limit chemotherapy for patients over 70years. Vinorelbine and paclitaxel are effective as single agents in advanced NSCLC. This phase II study evaluates safety and efficacy of a combination of these two agents in patients >70years with advanced NSCLC. MATERIALS AND METHODS: Patients with treatment naïve metastatic NSCLC received two cycles comprising 6 weekly doses of vinorelbine and paclitaxel, with restaging scans at week 8. Patients with radiographic progression came off study. The estimated sample size was 29. Toxicity analyses were conducted after 10 patients and again after 19 patients were enrolled. Outcomes were safety and efficacy, progression free (PFS) and overall survival (OS) and quality of life (QOL). RESULTS: The study closed at second interim analysis as 6/19 patients had ≥grade 4 non-hematologic toxicity (respiratory failure, sepsis, ischemic encephalopathy, pneumonia, hypoxemia, cardiopulmonary arrest, neutropenic fever, death). Of the 16 evaluable patients, 7 completed the study. Disease control rate (partial response+stable disease) was 47% (n=9); 37% (n=7) progressed. No complete responses were seen. Median PFS was 3.5months (95% CI: 1.4, 5.5) and OS 7.8months (95% CI: 1.9, 13.6). QOL did not change compared to baseline, at week 9, but increased at week 17. CONCLUSIONS: Although the combination met its response end points, increased toxicity makes this combination unsuitable for older patients. While QOL improved over the study, the small sample hinders interpretation.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Squamous Cell/drug therapy , Lung Neoplasms/drug therapy , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Aged , Aged, 80 and over , Anemia/chemically induced , Brain Ischemia/chemically induced , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathology , Chemotherapy-Induced Febrile Neutropenia/etiology , Disease-Free Survival , Early Termination of Clinical Trials , Female , Heart Arrest/chemically induced , Humans , Hypoxia/chemically induced , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Lymphopenia/chemically induced , Male , Neutropenia/chemically induced , Paclitaxel/administration & dosage , Pneumonia/chemically induced , Quality of Life , Respiratory Insufficiency/chemically induced , Survival Rate , Tomography, X-Ray Computed , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine
4.
Int J Hepatol ; 2012: 859076, 2012.
Article in English | MEDLINE | ID: mdl-22655201

ABSTRACT

The hepatocellular carcinoma (HCC) is one of the most common malignant tumors and carries a poor survival rate. The management of patients at risk for developing HCC remains challenging. Increased understanding of cancer biology and technological advances have enabled identification of a multitude of pathological, genetic, and molecular events that drive hepatocarcinogenesis leading to discovery of numerous potential biomarkers in this disease. They are currently being aggressively evaluated to establish their value in early diagnosis, optimization of therapy, reducing the emergence of new tumors, and preventing the recurrence after surgical resection or liver transplantation. These markers not only help in prediction of prognosis or recurrence but may also assist in deciding appropriate modality of therapy and may represent novel potential targets for therapeutic interventions. In this paper, a summary of most relevant available data from published papers reporting various tissue and serum biomarkers involved in hepatocellular carcinoma was presented.

6.
Clin Colorectal Cancer ; 10(2): 85-96, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21859559

ABSTRACT

PHY906 is a novel Chinese herbal preparation that has been used in the Orient for over 1800 years to treat a wide range of gastrointestinal side effects including diarrhea, abdominal cramps, vomiting, fever, and headache. Preclinical and clinical studies were conducted to further investigate the biologic and clinical activities of this herbal medicine. To ensure standardization and maintain interbatch reliability of PHY906, high performance liquid chromatography (HPLC) was used to establish a "chemical fingerprint" of PHY906. In vivo preclinical studies using the murine Colon 39 tumor model showed that PHY906 protected against the weight loss associated with irinotecan treatment. In the presence of PHY906, mice were able to tolerate otherwise lethal doses of irinotecan. Significantly improved antitumor activity and overall survival were observed in animals treated with the combination of irinotecan and PHY906 versus irinotecan alone. The combination of PHY906 with irinotecan, 5-fluorouracil (5-FU), and leucovorin (LV) also resulted in at least additive antitumor activity with no increased host toxicity. Based on these in vivo studies, a phase I multicenter, double-blind, randomized, placebo-controlled, dose escalation, cross-over study of PHY906 as a modulator of the weekly, bolus regimen of irinotecan, 5-FU, and LV (IFL) in the first-line treatment of patients with advanced colorectal cancer (CRC) was conducted. The specific objectives of this clinical trial were to determine the safety and tolerability of PHY906 when administered concomitantly with the bolus, weekly IFL regimen. Treatment with PHY906 did not alter the pharmacokinetics of 5-FU, irinotecan, or the irinotecan metabolite SN-38.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Colorectal Neoplasms/drug therapy , Drugs, Chinese Herbal/administration & dosage , Phytotherapy/methods , Adult , Aged , Animals , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Camptothecin/pharmacokinetics , Cross-Over Studies , Dose-Response Relationship, Drug , Double-Blind Method , Drugs, Chinese Herbal/adverse effects , Drugs, Chinese Herbal/pharmacokinetics , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/pharmacokinetics , Half-Life , Humans , Irinotecan , Leucovorin/administration & dosage , Leucovorin/adverse effects , Leucovorin/pharmacokinetics , Male , Mice , Middle Aged
7.
Clin Colorectal Cancer ; 10(3): 151-6, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21855035

ABSTRACT

Vascular endothelial growth factor (VEGF) signaling is considered to be one of the key factors involved in tumor-associated angiogenesis. Inhibition of angiogenesis has significantly improved anticancer therapy making it one of the cornerstones of treatment for various solid tumors. Several antiangiogenesis inhibitory compounds (eg, bevacizumab, sunitinib, sorafenib) are now widely used in the treatment of patients with colorectal, non-small-cell lung, advanced renal cell, hepatocellular, and breast cancer. One of the most commonly observed side effects of inhibition of VEGF signaling is hypertension, which is dose-dependent and varies in incidence among the different angiogenesis inhibitor drugs. Poorly controlled hypertension not only can lead to cardiovascular events, renal disease, and stroke, but may also necessitate discontinuation of anticancer therapy, thereby potentially limiting overall clinical benefit. In contrast, hypertension induced by VEGF inhibitors has been shown to represent an important pharmacodynamic biomarker of oncologic response. For the practicing oncologist, knowledge and optimal management of this toxicity is essential. Because of the lack of controlled studies on this topic, no clear recommendations are available. In this article, we review the available preclinical and clinical data on the pathogenesis and management of hypertension resulting from anti-VEGF inhibitor therapy and propose a treatment algorithm that our group has now implemented for daily clinical practice.


Subject(s)
Algorithms , Angiogenesis Inhibitors/therapeutic use , Hypertension/drug therapy , Neovascularization, Pathologic/prevention & control , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Animals , Humans , Signal Transduction
9.
Clin Colorectal Cancer ; 9(5): 315-8, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21208847

ABSTRACT

INTRODUCTION: Cetuximab therapy has been effectively combined with cytotoxic chemotherapy in the first-, second-, and third-line treatment settings. In general, treatment with cetuximab is well tolerated, though it has been associated with the development of hypersensitivity reactions (HSRs). In the case of severe HSRs, further therapy with cetuximab is not possible. In contrast with cetuximab, HSRs have been rarely observed with panitumumab therapy. Currently, panitumumab is indicated for patients with metastatic colorectal cancer (mCRC) with progressive refractory disease, and there is recent evidence documenting its clinical efficacy with cytotoxic chemotherapy in the first-line and second-line settings. However, the safety and efficacy of panitumumab after progression with cetuximab has not been well documented. PATIENTS AND METHODS: We present a retrospective review of our experience in treating 15 patients with mCRC who tolerated panitumumab with clinical benefit after failure on cetuximab therapy from November 2006 through September 2008 at the Yale Cancer Center in New Haven, CT and at the Saint Francis Cancer Treatment Center in Grand Island, NE. KRAS status was retrospectively assessed in patients with readily available tumor tissue. RESULTS: All 15 patients were treated with a standard dose of panitumumab 6 mg/kg intravenously every 2 weeks. No patient received premedication therapy. Of the 15 patients treated, 4 received only 2 doses of panitumumab but stopped further therapy because of deterioration in performance status. Of the 11 evaluable patients, we noted minor radiographic responses (Response Evaluation Criteria in Solid Tumors) in 3 patients and stable disease (SD) in 3 other patients after 8 weeks of therapy. Five patients had evidence for progressive disease, and further therapy was stopped. The median duration of SD was 4 months (range, 2-8 months). Among the 11 evaluable patients, 1 patient achieved > 50% reduction in carcinoembryonic antigen (CEA; 112 to 49 U/L), 3 patients had a 25% reduction (59 to 43 U/L, 84 to 61 U/L, and 67 to 42 U/L), and 1 patient had minor reduction in CEA (98 to 83 U/L). All patients tolerated panitumumab well with no occurrence of hypersensitivity reactions. Grade 3/4 toxicities were skin rash in 5 patients and asthenia in 1 patient. The other adverse events observed included grade 1-2 skin rash in 2 patients, grade 2 paronychia in 4 patients, grade 2 hypomagnesemia in 2 patients, and fatigue in 3 patients. One patient had wild-type KRAS, and this individual experienced a minor response to antibody therapy with > 50% reduction in CEA. A second patient was found to have mutant KRAS and, in terms of clinical response, this patient experienced SD for 6 months. The third patient evaluated had mutant KRAS, and this individual was unable to tolerate more than 2 doses and was therefore not evaluable for response. CONCLUSION: Panitumumab may represent an alternative treatment strategy for patients with refractory mCRC who have experienced failure with standard therapy including cetuximab-based regimens. Our relatively small clinical experience suggests that cetuximab and panitumumab may exert their antitumor activity through different mechanisms; however, further work is required to investigate this potentially interesting issue.


Subject(s)
Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , Drug Resistance, Neoplasm/drug effects , Liver Neoplasms/drug therapy , Salvage Therapy , Antibodies, Monoclonal, Humanized , Cetuximab , Colorectal Neoplasms/pathology , Disease Progression , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/immunology , Follow-Up Studies , Humans , Liver Neoplasms/secondary , Panitumumab , Retrospective Studies , Survival Rate , Treatment Outcome
11.
Croat Med J ; 46(3): 458-62, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15861527

ABSTRACT

Primary cutaneous T- and B-cell lymphomas are a heterogeneous group of diseases with varied clinical presentations and prognosis. The use of new molecular, histological, and clinical criteria has improved their recognition. Cutaneous B-cell and T-cell lymphomas are seldom found together in the same patient. Here we report a rare case of mycosis fungoides variant of a cutaneous T-cell lymphoma (CTCL) which later developed Epstein-Barr virus (EBV) associated cutaneous B-cell lymphoproliferative disorder. The patient initially presented with generalized erythroderma, extensive plaques, and axillary lymphadenopathy. Histopathology and immunophenotyping of her tumor from the right breast nodule revealed a T-cell lymphoma consistent with mycosis fungoides. She was initially treated with pentostatin, followed by topical mechlorethamine and topical steroids. After progression of her mycosis fungoides with worsening diffuse skin lesions on this regimen, her treatments were changed to oral bexarotene with an initial partial response followed by stable disease. Three years from her initial presentation, she developed ulcerated cauliflower-like nodules on her forehead. Biopsy of these lesions revealed EBV-positive large- and medium-sized pleomorphic B-cells consistent with EBV-driven B-cell lymphoproliferative disorder. She was treated with topical acyclovir cream on the involved skin areas while continuing with oral bexarotene for mycosis fungoides. Skin lesions gradually diminished and totally disappeared after four weeks of topical acyclovir treatment. Bexarotene treatment was continued for another year until the mycosis fungoides progressed and became wide spread causing her death four and a half years after the initial diagnosis. The coexistence of two cutaneous non-Hodgkin lymphomas of different lineage in the same patient and the complete clinical response of EBV-related B-cell cutaneous component to topical acyclovir makes this rare case particularly interesting.


Subject(s)
Acyclovir/therapeutic use , Antiviral Agents/therapeutic use , Epstein-Barr Virus Infections/drug therapy , Lymphoma, B-Cell/drug therapy , Administration, Topical , Epstein-Barr Virus Infections/complications , Female , Herpesvirus 4, Human/isolation & purification , Humans , Lymphoma, B-Cell/complications , Lymphoma, B-Cell/virology , Middle Aged , Mycosis Fungoides/complications , Skin Neoplasms/complications
12.
Leuk Lymphoma ; 45(5): 1071-6, 2004 May.
Article in English | MEDLINE | ID: mdl-15291370

ABSTRACT

Composite lymphomas constitute the presence of two different types of non-Hodgkin lymphoma or Hodgkin and non-Hodgkin lymphoma at the same anatomic site. We report an unusual case of a 73-year-old woman who initially presented with a composite lymphoma of chronic lymphocytic leukemia (CLL) and follicular lymphoma. After 5 years of follow-up and intermittent treatment, she developed Hodgkin disease with diffuse liver involvement. Biopsy of the liver showed Reed-Sternberg cells with typical morphology and immunophenotype. While fluorescent in situ hybridization (FISH) analyses for t(14;18) were positive in the lymph node tissue with follicular lymphoma, we were unable to show the same in the liver biopsy specimen. Here, we describe the clinical, morphologic, immunophenotypic, and cytogenetic features of this unusual composite lymphoma case involving CLL and follicular lymphoma, with the subsequent development of a Hodgkin lymphoma.


Subject(s)
Hodgkin Disease/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Lymphoma, Follicular/complications , Lymphoma/classification , Aged , Cytogenetic Analysis , Female , Hodgkin Disease/diagnosis , Hodgkin Disease/etiology , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Liver Neoplasms/pathology , Lymph Nodes/pathology , Lymphoma/pathology , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/pathology , Neoplasms, Second Primary , Retroperitoneal Neoplasms/pathology
16.
Clin Colorectal Cancer ; 1(3): 179-180, 2001 Nov.
Article in English | MEDLINE | ID: mdl-12450433

ABSTRACT

No Abstract

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