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Biomedical subjects

Luis E Raez

Publications and source records attributed to Luis E Raez.

At least 19 recordsLinked to original sources
PubMed2006

Randomized phase II study of bortezomib alone and bortezomib in combination with docetaxel in previously treated advanced non-small-cell lung cancer.

PURPOSE: To evaluate the efficacy and toxicity of bortezomib +/- docetaxel as second-line therapy in patients with relapsed or refractory advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomly assigned to bortezomib 1.5 mg/m2 (arm A) or bortezomib 1.3 mg/m2 plus docetaxel 75 mg/m2 (arm B). A treatment cycle of 21 days comprised four bortezomib doses on days 1, 4, 8, and 11, plus, in arm B, docetaxel on day 1. Patients could receive unlimited cycles. The primary end point was response rate. RESULTS: A total of 155 patients were treated, 75 in arm A and 80 in arm B. Baseline characteristics were comparable. Investigator-assessed response rates were 8% in arm A and 9% in arm B. Disease control rates were 29% in arm A and 54% in arm B. Median time to progression was 1.5 months in arm A and 4.0 months in arm B. One-year survival was 39% and 33%, and median survival was 7.4 and 7.8 months in arms A and B, respectively. Adverse effect profiles were as expected in both arms, with no significant additivity. The most common grade > or = 3 adverse events were neutropenia, fatigue, and dyspnea (4% and 53%, 19% and 26%, and 17% and 14% of patients in arms A and B, respectively). CONCLUSION: Bortezomib has modest single-agent activity in patients with relapsed or refractory advanced NSCLC using this schedule, with minor enhancement in combination with docetaxel. Additional investigation of bortezomib in NSCLC is warranted in combination with other drugs known to be active, or using different schedules.

Adult↗
PubMed2006

Efficacy and safety of oxaliplatin and docetaxel in patients with locally advanced and metastatic non-small-cell lung cancer (NSCLC).

BACKGROUND AND AIMS: Platinum-based doublets are recommended as treatment for advanced or metastatic non-small-cell lung cancer (NSCLC); however, chemotherapy must be tailored to limit side effects. A phase II study was conducted to evaluate the efficacy and safety of oxaliplatin combined with docetaxel for NSCLC. METHODS: Patients with stage IIIB or IV, chemotherapy-naive NSCLC received docetaxel 70 mg/m(2), oxaliplatin 130 mg/m(2), and pegfilgrastim 6 mg every 21 days for up to six cycles. Primary endpoint was overall response rate (ORR), secondary endpoints were progression-free (PFS) and overall survival (OS), and safety. RESULTS: Twenty-nine patients were treated; 93% had stage IV disease and 28% had brain metastases. In 27 evaluable patients with follow-up, there were 10 partial responses for an ORR of 37% (90% confidence interval [CI], 22-55%). Median PFS was 4.6 months (95% CI, 2.6-6.5 months); 12-month PFS was 14.8% (95% CI, 3.4-34.0%). Median OS was 10.9 months (95% CI, 8.9-16.8 months); 12-month OS was 40% (95% CI, 19-61%) and 18-month OS was 16% (95% CI, 1-46%). In 29 treated patients, there were no unusual or unexpected adverse events. The most common grade 3 and 4 toxicities were anemia (14% of patients) and hyperglycemia (10%); there were only two reports of neutropenia; both were grade 1 or 2. CONCLUSION: These phase II findings suggest that the combination of oxaliplatin and docetaxel is active and well tolerated, and should be further investigated as a feasible treatment alternative for patients with advanced or metastatic NSCLC.

Adult↗
PubMed2006

Heat shock protein-based cancer vaccines.

The ability to duplicate the remarkable success of infectious disease vaccines in cancer, with durably robust and highly specific antitumor immune responses, has been long held as one of the keys in developing true "magic bullet" cancer therapies. This article attempts to explain why cancer vaccines have failed (so far), delineate the increasingly complex barriers that prevent the eliciting of effective antitumor immunity and examines the ability of heat shock protein-based vaccines to overcome these barriers. This article is not a definitive compendium of the huge body of relevant literature but rather focuses on the major concepts underlying active specific immunotherapy in general and heat shock protein vaccines in particular.

Antigen-Presenting Cells↗
PubMed2006

Current results and future applications of radioimmunotherapy management of non-Hodgkin's lymphoma.

Monoclonal antibodies labeled with radionuclides have become an important therapeutic tool in the treatment of patients with non-Hodgkin's lymphomas (NHL). At the present time, their use in the US is approved for patients with rituximab-resistant, low-grade, follicular or transformed NHL. Encouraging responses seen in the relapsed and refractory patients have prompted their evaluation in earlier disease or in other histologic sub-types either alone or in combination with conventional chemotherapy. Additionally, they have been included as preparative regimens for stem cell transplant protocols within the context of clinical trials. This review discusses the latest clinical trials and future directions of radioimmunoconjugates in the treatment of NHL, with emphasis on US Food and Drug Administration (FDA) approved radioimmunoconjugates, namely 131I-tositumomab and 90Y-ibritumomab tiuxetan.

Antibodies, Monoclonal↗
PubMed2006

New developments in chemotherapy for advanced non-small cell lung cancer.

PURPOSE OF REVIEW: The treatment of patients with advanced non-small cell lung cancer has changed considerably in the past decade. This paper reviews the most significant changes seen in chemotherapy and the most promising new agents in development for this disease. RECENT FINDINGS: Chemotherapy prolongs survival and improves quality of life in patients with a good performance status and appears to alleviate disease-related symptoms in patients with a lower performance status. Platinum-based regimens became standard; none of the third-generation drug combinations seemed to be superior to the others. Nonplatinum combinations are reasonable alternatives now and offer a better toxicity profile in certain populations. Attempts to add molecular-targeted therapy to combination chemotherapy have failed except for bevacizumab. New compounds such as pemetrexed, bortezomib, TLK286, bevacizumab, and the epothilones are currently being evaluated in non-small cell lung cancer. SUMMARY: Management of non-small cell lung cancer has improved considerably in the past decade. The overall benefit of chemotherapy over supportive care has been shown, platinum-based doublets have been established, nonplatinum regimens have been developed, chemotherapy has been used more broadly in subgroups of patients who have been previously neglected, and a shorter chemotherapy duration has been shown to be equally effective. After hitting a plateau in the benefit of chemotherapy, new drugs with novel action mechanisms such as the ones described here offer hope to improve therapy for this disease.

Antineoplastic Agents↗
PubMed2006

Successful treatment of autoimmune hepatitis and idiopathic thrombocytopenic purpura with the monoclonal antibody, rituximab: case report and review of literature.

Rituximab, a chimeric monoclonal anti-CD20 antibody, has shown activity in several autoimmune disorders. We describe a case of a 52 years old female who was diagnosed with idiopathic thrombocytopenic purpura and concomitant autoimmune hepatitis (AIH), both non-responsive to steroids. She was subsequently treated with rituximab, which resulted in a rapid increase in her platelet count and an unexpected normalization of her hepatic biochemical tests. Both her platelet count and her hepatic biochemical tests remained normal for over 5 months. In this case, rituximab showed an impressive clinical response for the treatment of AIH, and it may be considered as an alternative treatment in patients who do not respond to corticosteroid therapy. Prospective randomized studies in AIH are needed to validate this observation.

Antibodies, Monoclonal↗
PubMed2006

Present and future of lung cancer vaccines.

New approaches are needed to improve the current treatment of lung cancer. Inducing an immune response against lung tumour cells with vaccines represents an attractive therapy. However, lung tumours had not been considered good targets for vaccine therapy and, therefore, immune approaches have not been studied extensively in this setting. Current experimental strategies for antitumour vaccines include the generation of active immune responses against specific tumour antigens. Understanding the mechanisms of antitumour immunity and identifying relevant tumour-specific antigens will probably improve therapeutic strategies and provide avenues for the future of lung cancer therapy. There have been a number of preclinical immunotherapy trials suggesting activity, and a smaller number of human clinical trials using various vaccines in lung cancer. Initial data from these trials have shown preliminary evidence of induction of immune responses and suggest clinical activity. This paper reviews some of the most important developments in vaccines for lung cancer.

Animals↗
PubMed2006

Induction chemotherapy in the management of squamous cell carcinoma of the head and neck.

Platinum-based chemotherapy administered concurrently with radiation has been adopted as the standard treatment for locally advanced head and neck squamous cell carcinoma. Historically, randomized trials using induction chemotherapy prior to radiation therapy alone have failed to demonstrate a clear survival advantage, and concurrent chemoradiation has delivered better results than previously obtained with radiation therapy alone, establishing the benefit of adding chemotherapy. This method of treatment, together with new modalities of therapy and novel agents, has reintroduced the question of induction chemotherapy before definitive chemoradiation. Systemic chemotherapy offers a better possibility of reducing systemic metastasis and improving cosmetic appearance. This article reviews developing trends using induction chemotherapy followed by chemoradiation in patients with head and neck squamous cell carcinoma.

Antineoplastic Agents↗
PubMed2005

Pemetrexed-associated urticarial vasculitis.

Pemetrexed (Alimta, Eli Lilly and Company, Indianapolis, IN) is a structurally novel anti-folate agent. The United States Food and Drug Administration has approved pemetrexed for the treatment of patients with malignant pleural mesothelioma and previously treated patients with locally advanced or metastatic non-small cell lung cancer. In the phase III trials that led to its approval, rash was reported in 17 and 22% of patients receiving pemetrexed alone or in combination with cisplatin. However, little has been published about the characteristics of this rash or about its mechanism. In an attempt to contribute to the growing body of knowledge about this new agent, we describe a case in which a patient developed a rash secondary to urticarial vasculitis associated with pemetrexed.

Aged↗
PubMed2005

Clinical trials targeting lung cancer with active immunotherapy: the scope of vaccines.

Successful active immunotherapy is expected to be specific and nontoxic. Until now, the success of immunotherapy in cancer has been sporadic and unpredictable. This has been attributable in part to the lack of a full understanding of the mechanistic underpinnings of immune regulation. Furthermore, the lack of systematic success of immunotherapy, as argued in this review, stems from failing to effectively target tumors such as non-small cell lung cancer. In this review, the rationale and design for induction of immunity to non-small cell lung cancer and clinical trials of the most important lung cancer vaccines in development are discussed.

Antigens, Neoplasm↗
PubMed2005

DNA methylation: its role in lung carcinogenesis and therapeutic implications.

A new era in the treatment of malignant diseases has been observed through the use of biologic agents targeting growth factor receptors, signaling pathways, gene mutations and others. The results have been impressive in some diseases and modest in others. The discovery of new targets has expanded our knowledge of different mechanisms in tumorigenesis. One of these mechanisms has been DNA methylation, which is an important gene transcription regulator. Although the role of methylation in lung carcinogenesis is not well understood, there is an enormous quantity of evolving data suggesting its critical role in lung cancer. In this review, the authors will discuss methylation in lung carcinogenesis and its possible clinical implications.

Apoptosis Regulatory Proteins↗
PubMed2005

Lung cancer immunotherapy.

Recent insights into anti-tumor immunotherapy have led to a wave of clinical trials involving immunotherapy for lung cancer. Vaccines have evolved from nonspecific immune stimulants, like Bacillus Calmette-Guerin (BCG), to much more specific and potent strategies, some of which generate active immune responses against tumor-associated antigens. Understanding the mechanisms of anti-tumor immunity and identifying target antigens will likely improve these therapeutic strategies and provide them with a niche in the future of lung cancer therapy.

Animals↗
PubMed2004

The utility of a bone marrow biopsy in diagnosing the source of fever of unknown origin in patients with AIDS.

A bone marrow (BM) aspiration and biopsy is often believed to be a needed diagnostic procedure in the work-up of patients with fever of unknown origin (FUO), especially in the setting of AIDS. Is it worthwhile to proceed with this invasive diagnostic method? Clinical information obtained on 104 patients in whom AIDS had been previously diagnosed and who had been admitted with a presumptive diagnosis of FUO was retrospectively analyzed. Seventy-two cases met the inclusion criteria. A BM aspiration and biopsy had a low sensitivity as a diagnostic tool even in patients who had abnormal hematologic parameters. BM biopsy was also not helpful in diagnosing non-Hodgkin lymphoma (NHL) cases in this study. Although the incidence of NHL has risen since the emergence of HIV, the predominant types of lymphoma seen in AIDS patients are intermediate/high-grade lymphomas rather than low grade, and consequently, the incidence of BM involvement is low, decreasing the sensitivity of a BM biopsy as a diagnostic tool. These observations were validated in this study. The majority of BM biopsies in this series revealed diagnostic features of infections. This observation can likely be related to the high prevalence of HIV/AIDS patients in this community and opportunistic infections associated with this disease.

AIDS-Related Opportunistic Infections↗
PubMed2004

Allogeneic vaccination with a B7.1 HLA-A gene-modified adenocarcinoma cell line in patients with advanced non-small-cell lung cancer.

PURPOSE: To determine the safety, immunogenicity, and clinical response to an allogeneic tumor vaccine for non-small-cell lung cancer, we conducted a phase I trial in patients with advanced metastatic disease. PATIENTS AND METHODS: We treated 19 patients with a vaccine based on an adenocarcinoma line (AD100) transfected with B7.1 (CD80) and HLA A1 or A2. Patients were vaccinated intradermally with 5 x 10(7) cells once every 2 weeks. Three vaccinations represented one course of treatment. If patients had complete response, partial response, or stable disease, they continued with the vaccinations for up to three courses (nine vaccinations). Immune response was assessed by a change between pre-study and postvaccination enzyme-linked immunospot frequency of purified CD8 T-cells secreting interferon-gamma in response to in vitro challenge with AD100. RESULTS: Four patients experienced serious adverse events that were unrelated to vaccine. Another four patients experienced only minimal skin erythema. All but one patient had a measurable CD8 response after three immunizations. The immune response of six surviving, clinically responding patients shows that CD8 titers continue to be elevated up to 150 weeks, even after cessation of vaccination. Overall, one patient had a partial response, and five had stable disease. Median survival for all patients is 18 months (90% CI, 7 to 23 months), with corresponding estimates of 1-year, 2-year, and 3-year survival of 52%, 30%, and 30%, respectively. HLA matching of vaccine, age, sex, race, and pathology did not bear a significant relation to response. CONCLUSION: Minimal toxicity and good survival in this small population suggest clinical benefit from vaccination.

Adenocarcinoma↗
PubMed2004

Chemotherapy for advanced non-small-cell lung cancer.

The management of patients with advanced non-small-cell lung cancer has changed considerably in the last decade. Chemotherapy prolongs survival and improves quality of life in patients with a good performance status and appears to improve disease-related symptoms in patients with a lower performance status. Platinum-based doublets remain the standard regimen, but nonplatinum combinations are reasonable alternatives. Newer agents with novel mechanisms of action have opened new areas of clinical research and are likely to further improve the outcome of patients with advanced non-small-cell lung cancer.

Antibodies, Monoclonal↗