Biography:

In the past Chandra P. Belani has collaborated on articles with Arjun Pennathur and Cesare Gridelli. One of their most recent publications is Original articleGeneral thoracicLong-Term Results of a Phase II Trial of Neoadjuvant Chemotherapy Followed by Esophagectomy for Locally Advanced Esophageal Neoplasm. Which was published in journal The Annals of Thoracic Surgery.

More information about Chandra P. Belani research including statistics on their citations can be found on their Copernicus Academic profile page.

Chandra P. Belani's Articles: (28)

Original articleGeneral thoracicLong-Term Results of a Phase II Trial of Neoadjuvant Chemotherapy Followed by Esophagectomy for Locally Advanced Esophageal Neoplasm

BackgroundEffective systemic therapy is considered essential to improve the outcome for patients with surgically resectable locally advanced esophageal carcinoma. We report the long-term results of our phase II study of neoadjuvant chemotherapy, followed by esophagectomy and adjuvant chemotherapy for potentially resectable esophageal carcinoma.MethodsPatients were staged with computed tomography scan (n = 70), endoscopic ultrasonography (n = 63), and laparoscopy with or without thoracoscopy (n = 70). The pretreatment stages were T2N0 (n = 1), T2N1 (n = 15), T3N0 (n = 13), and T3N1 (n = 41). Chemotherapy consisted of 2 or 3 cycles of cisplatin, 5-fluorouracil, and paclitaxel followed by esophagectomy and adjuvant chemotherapy. Patients were monitored for recurrence and survival.ResultsA total of 70 patients were enrolled (66 adenocarcinoma, 4 squamous cell carcinoma; 64 men and 6 women; median age, 60 years). Esophagectomy was performed in 63 patients. Operative mortality was 0%. The median overall survival of the entire group was 27.4 months. Seventeen patients were alive at a median follow-up of 62.8 months (range, 39.1 to 142). Fourteen patients were alive without recurrence at a median follow-up of 79 months (range, 39 to 138). Nodal status was an important predictor of overall survival. Patients who were downstaged experienced a significantly improved median survival of 63.4 months versus 21.5 months and overall survival (p = 0.005).ConclusionsThis prospective study for esophageal carcinoma demonstrates encouraging long-term results. In particular, downstaging of the tumor with preoperative chemotherapy is predictive of better long-term outcome. Our results support the role for perioperative chemotherapy for locally advanced resectable esophageal cancer.

Paclitaxel and Docetaxel Combinations in Non-Small Cell Lung Cancer

Paclitaxel, the first of the taxanes, has exhibited unique andencouraging single-agent activity in the treatment of non-small celllung cancer (NSCLC). Yet, with single-agent response rates approaching25%, it was logical to examine the impact of paclitaxel in combinationchemotherapy regimens. In trials evaluating the activity of paclitaxelin combination with one of the platinum compounds, cisplatin orcarboplatin, response rates have ranged from 35 to > 50% and weresignificantly better than response rates observed withetoposide/cisplatin, the previous standard regimen for treatment of NSCLC. Docetaxel is a newer taxane that also has exhibited notablesingle-agent activity and response rates ranging from 20 to 50% whencombined with cisplatin. Future research will look to refine the use oftaxane combinations in NSCLC and to examine the potential of theseunique and promising drugs when combined with newer agents that areactive against this disease.

Recent updates in the clinical use of platinum compounds for the treatment of lung, breast, and genitourinary tumors and myeloma

Platinum compounds have shown activity in a broad spectrum of human tumors in vitro and in vivo. The clinical utility of platinum agents in gynecologic and gastrointestinal cancers (particularly oxaliplatin in colorectal cancer) has been well documented and platinum agents continue to be evaluated in a variety of other cancers. Given preclinical evidence of synergy among some platinum compounds and new anticancer agents, clinical trials exploring platinum-based combination therapies may yield improved treatment for a variety of malignancies. Recent clinical data on new chemotherapeutic strategies for the treatment of lung, breast, and genitourinary cancers and myeloma will be presented in this review.

Adjuvant and neoadjuvant therapy in non-small cell lung cancer

The 5-year survival rates for patients with non-small cell lung cancer (NSCLC) ranges from 9% to 61% following resection, depending on clinical stage; survival rates post-surgery (pathologic stage) range from 25% to 67%. Most stage I and II patients eventually experience recurrent disease: two thirds occur systemically, one third locally. Surgical resection remains the standard of care in early stage NSCLC, although the role of surgery in stage IIIA [N2] disease is controversial. Despite resection, the vast majority of lung cancer patients will experience recurrent and/or metastatic disease; therefore, supplementing surgery with adjuvant therapy is a rational treatment strategy. Recent data indicate that adjuvant chemotherapy should now be considered the standard of care for the treatment of patients with completely resected early stage NSCLC, with the single exception of patients with stage IA disease, where the prognosis is relatively favorable and there is currently no evidence supporting the efficacy of adjuvant therapy. While recent data from trials of adjuvant chemotherapy have shown promising results, no study has yet compared the utility of adjuvant versus neoadjuvant, or induction, chemotherapy. From the current data, more than 90% of patients receiving neoadjuvant chemotherapy undergo the planned surgical resection. Neoadjuvant chemotherapy may also downstage the disease before surgery and decrease perioperative tumor seeding, and molecularly targeted approaches with neoadjuvant therapy appear promising.

Optimizing chemotherapy for advanced non-small cell lung cancer: focus on docetaxel

SummarySystemic chemotherapy with platinum-based combinations provides modest improvements in both survival and quality of life for patients with advanced non-small cell lung cancer (NSCLC). For first-line treatment of advanced NSCLC patients with a good performance status, the accepted standard of care is a platinum agent combined with docetaxel, paclitaxel, gemcitabine, vinorelbine or irinotecan. Several studies have attempted to identify an optimal platin-based regimen, however, all regimens offer some combination of clinical benefit with characteristic toxicities and no regimen appears clearly superior. Non-platinum regimens have also shown equivalent efficacy compared to platinum combinations, but again, none are clearly superior. Most recently, the existing standard of care is being amended to reflect the survival advantage gained from adding a new targeted agent, bevacizumab, to traditional platinum-doublet therapy for patients with non-squamous NSCLC. Docetaxel is the only agent currently approved for both first- and second-line treatment of advanced NSCLC. Multiple randomized clinical trials have established the efficacy of platin-docetaxel regimens for first-line treatment of advanced NSCLC. Improvements in various lung cancer related symptoms and global quality of life indices have also been noted with docetaxel-based regimens. Based on the efficacy of platin-docetaxel regimens in advanced disease, they are now being incorporated into the adjuvant and neoadjuvant treatment of early-stage disease.

ReviewWomen and lung cancer: Epidemiology, tumor biology, and emerging trends in clinical research

SummaryLung cancer is the leading cause of cancer-related death in both men and women. Environmental carcinogens, particularly tobacco smoke, play a dominant role in the development of lung cancer, although 10–15% of all patients diagnosed are non-smokers. In addition, emerging data demonstrate sex-specific differences in lung cancer susceptibility and prognosis. This implies that the development of lung cancer is modulated by complex interactions between genetic, hormonal, behavioral, and environmental factors. A better understanding of the differences between men and women and their impact on the prevention, diagnosis, and treatment of lung cancer requires continued basic and clinical research. Recent data on the epidemiological aspects of lung cancer in women, lung tumor biology, and emerging trends in clinical research were presented at a thought leaders’ roundtable hosted by the Society for Women's Health Research. The panel concluded that as the patient population in lung cancer is changing from mostly male smokers to include women and non-smokers, an urgent need exists to increase awareness and research funding to improve lung cancer care, particularly in women. To further improve survival in this disease, both clinical characteristics and tumor biology should be considered in the development of new treatment options.

ReviewMaintenance treatment of advanced non-small-cell lung cancer: Results of an International Expert Panel Meeting of the Italian Association of Thoracic Oncology

AbstractSeveral randomized trials have recently investigated the role of maintenance treatment for patients with advanced non-small-cell lung cancer (NSCLC) with responding or stable disease after completion of first-line chemotherapy. Maintenance strategy has relevant implications in terms of potential toxicity, logistics and costs, and all of these aspects should be taken into account, together with the magnitude of benefit for the patient. In order to assess the strengths and limitations of available evidence, to help clinical practice, and to suggest priorities for future clinical research, the Italian Association of Thoracic Oncology (AIOT) organized an International Experts Panel Meeting on maintenance treatment of advanced NSCLC, which took place in Sperlonga (Italy) in May 2011. Based on the available evidence, panelists agreed that maintenance therapy represents a treatment option in advanced NSCLC. Maintenance should be discussed with patients not progressed after 4–6 cycles of first-line chemotherapy, who are fit (performance status 0–1) and without persistent chemotherapy-induced toxicity. Patients need to be well informed about potential advantages and disadvantages of accepting additional therapy without a “treatment-free period”. Two different strategies, switch or continuation maintenance, are supported by available evidence. At the moment, there is no direct comparison between switch maintenance and continuation maintenance. For future trials, the panel recommends the use of overall survival as the primary endpoint, with pre-defined second-line treatment. Translational research is essential to identify predictive factors, and should be performed, whenever feasible, in order to achieve treatment optimization with proper patient selection.

Critical ReviewSurgical Management of Early-Stage Non-small Cell Lung Carcinoma and the Present and Future Roles of Adjuvant Therapy: A Review for the Radiation Oncologist

We review the evidence for optimal surgical management and adjuvant therapy for patients with stages I and II non-small cell lung cancer (NSCLC) along with factors associated with increased risks of recurrence. Based on the current evidence, we recommend optimal use of mediastinal lymph node dissection, adjuvant chemotherapy, and post-operative radiation therapy, and make suggestions for areas to explore in future prospective randomized clinical trials.

Clinical InvestigationNational Cancer Database Analysis of Proton Versus Photon Radiation Therapy in Non-Small Cell Lung Cancer

PurposeTo analyze outcomes and predictors associated with proton radiation therapy for non-small cell lung cancer (NSCLC) in the National Cancer Database.Methods and MaterialsThe National Cancer Database was queried to capture patients with stage I-IV NSCLC treated with thoracic radiation from 2004 to 2012. A logistic regression model was used to determine the predictors for utilization of proton radiation therapy. The univariate and multivariable association with overall survival were assessed by Cox proportional hazards models along with log–rank tests. A propensity score matching method was implemented to balance baseline covariates and eliminate selection bias.ResultsA total of 243,822 patients (photon radiation therapy: 243,474; proton radiation therapy: 348) were included in the analysis. Patients in a ZIP code with a median income of <$46,000 per year were less likely to receive proton treatment, with the income cohort of $30,000 to $35,999 least likely to receive proton therapy (odds ratio 0.63 [95% confidence interval (CI) 0.44-0.90]; P=.011). On multivariate analysis of all patients, non-proton therapy was associated with significantly worse survival compared with proton therapy (hazard ratio 1.21 [95% CI 1.06-1.39]; P<.01). On propensity matched analysis, proton radiation therapy (n=309) was associated with better 5-year overall survival compared with non-proton radiation therapy (n=1549), 22% versus 16% (P=.025). For stage II and III patients, non-proton radiation therapy was associated with worse survival compared with proton radiation therapy (hazard ratio 1.35 [95% CI 1.10-1.64], P<.01).ConclusionsThoracic radiation with protons is associated with better survival in this retrospective analysis; further validation in the randomized setting is needed to account for any imbalances in patient characteristics, including positron emission tomography–computed tomography staging.

Original StudyRandomized Phase II Trial of Concurrent Versus Sequential Bortezomib Plus Docetaxel in Advanced Non–Small-Cell Lung Cancer: A California Cancer Consortium Trial

AbstractBackgroundThe proteasome inhibitor bortezomib sensitizes tumor cells to chemotherapy-induced apoptosis. In preclinical non–small-cell lung cancer (NSCLC) models, p53-dependent growth arrest after bortezomib treatment resulted in reduced cytotoxicity if bortezomib preceded docetaxel. The reverse sequence of docetaxel before bortezomib was associated with increased apoptosis, cleavage of caspase-3 and PARP (poly [ADP-ribose] polymerase), and reduction in Bcl-2. A prospective randomized phase II trial of concurrent versus sequential docetaxel and bortezomib was conducted to assess whether administration sequence resulted in measurable clinical differences.Patients and MethodsPreviously treated patients with advanced NSCLC were randomized to concurrent (CON) or sequential (SEQ) docetaxel (75 mg/m2 intravenous [I.V.]) followed by bortezomib, every 3 weeks. In the CON arm, bortezomib (1.6 mg/m2 I.V.) was given on days 1 and 8, and in the SEQ arm, it was given on days 2 and 8. Previous erlotinib as well as treated or controlled brain metastases were allowed. The primary endpoint was objective response rate (RR); progression-free (PFS) and overall survival (OS) were secondary endpoints.ResultsEighty-one patients were randomized (40 CON and 41 SEQ). Grade 3+ toxicities were mostly due to myelosuppression. One patient each had grade 4 hyponatremia and syncope. Toxicities were similar between the arms. There was 1 treatment-related death in the SEQ arm. There were 8 partial responders, 4 in each arm, for an overall RR of 10%. Disease control rate was similar in both arms (50% vs. 49%). Median PFS was 12 weeks in the CON arm and 11 weeks in the SEQ arm. Median OS times in the CON and SEQ arms were 13.3 and 10.5 months, respectively.ConclusionDocetaxel plus bortezomib given sequentially or concurrently has similar RR and PFS. Median survival in the SEQ arm exceeds published survival estimates for either agent alone or in combination. Any further studies in this population would require molecular characterization of a phenotype most likely to benefit from proteasome inhibitor therapy.

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