Platinum based chemotherapy in elderly patients with non-small cell lung carcinoma (NSCLC): Experience from an Indian tertiary cancer center.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20528-e20528
Author(s):  
Aparna Sharma ◽  
Sachin Khurana ◽  
Raja Pramanik ◽  
Sunil Kumar ◽  
Sushmita Pathy ◽  
...  

e20528 Background: Instituting platinum based chemotherapy in elderly population is often associated with poor tolerance and attending toxicities. We present our limited center experience of chemotherapy in the geriatric population group. Methods: This is a retrospective single center experience of all registered patients in lung cancer clinic (LCC) in the department of medical oncology, Dr. B.R.A. IRCH, AIIMS. All histopathologically proven cases of NSCLC with age more than 70 years who received platinum based chemotherapy (single/doublet) with complete patient records were analysed. The study was carried out between November 2016 and August 2018.Data was analysed using STATA v13. Results: The cohort consisted of 25 patients who satisfied the inclusion criteria. Males comprised 84%(n = 21) of the cohort. Median age of study population was 72.7 years years (Range 70-84). 36%(n = 9) of the study population had one comorbidity while 8% (n = 2) had multiple comorbidities. 68% (n = 17) of the cohort were smokers. ECOG(Eastern cooperative oncology group) PS (performance status) 1 was seen in 48% (n = 12) and PS 2 in 32% (n = 8) and PS 3 in 16% (n = 4) respectively of the patients. Histopathologically, 48% (n = 12) of the population constituted squamous cell carcinoma while 40%(n = 10) had adenocarcinoma. 76%(n = 19) patients had Stage 4 NSCLC. Most common chemotherapy regimes used were weekly Paclitaxel carboplatin (n = 11, 44%), three weekly paclitaxel carboplatin (n = 8 , 32%) Pemetrexed carboplatin (n = 5, 20%) and gemcitabine carboplatin (n = 1, 4%). Only 12% (n = 3) could complete more than 4 cycles of chemotherapy and 3 could receive maintenance chemotherapy. Best responses according to RECIST (Response Evaluation Criteria In Solid Tumors) criteria v1.1 achieved were complete response in 12%(n = 3), partial response in 16% (n = 4), stable disease 24%(n = 6) and progressive disease in 48%(n = 12). Most common grade 3 and 4 adverse events according to CTCAE (common terminology criteria for adverse events) v4.03 were mucositis 29.17%(n = 7), diarrhea 12% (n = 3), peripheral neuropathy 12.5 (n = 3) and hematological toxicity 16%(n = 4). Conclusions: The patient number in this study cohort is limited.However, our experience demonstrates that abbreviated therapy in elderly subgroup is fairly well tolerated. Various tools like comprehensive geriatric assessment need to be utilized to provided tailored therapy in the elderly subgroup. A prospective study is required to address the efficacy and toxicity profile of chemotherapy in this select population.

2021 ◽  
pp. 096032712110594
Author(s):  
Harleen Kaur Walia ◽  
Navneet Singh ◽  
Siddharth Sharma

Background Genetic polymorphism within the P1 isoenzyme of the Glutathione-S-Transferase (GST) family is found to modulate and alter the enzyme activity of GSTP1 protein and thus may result in a change of sensitivity to platinum-based chemotherapy. We investigated the relationship between GSTP1 Ile 105 Val polymorphisms and overall survival, treatment response, and for both hematological and non-hematological toxicity of advanced North Indian lung cancer patients undergoing platinum-based double chemotherapy. Methods The polymorphism of GSTP1 Ile 105 Val in North Indian lung cancer patients was assessed by polymerase chain reaction-restriction fragment length polymorphism. A total of 682 lung cancer patients were enrolled in the study, and it was observed that patients who were carrying both the mutant alleles ( Val/Val) for the GSTP1 polymorphism showed a higher trend of median survival time (MST) as compared to the patients bearing the wild type of genotype (Ile/Ile) (MST = 8.30 vs. 7.47, p = 0.56). Based on toxicity profiling, we observed that lung cancer patients with the mutant genotype of GSTP1 (Val/Val) had an increased risk of leukopenia (OR = 2.41; 95% CI = 1.39-4.18, p = 0.001) as compared to subjects carrying both copies of the wild alleles (Ile/Ile). Our data suggested that patients with heterozygous genotype (Ile/Val) had a 2.14-fold increased risk of developing severe anemia (OR = 2.14, 95% CI = 0.97-4.62, p = 0.03). Our data also showed that in small cell lung carcinoma (SCLC) patients' polymorphism of GSTP1 was associated with thrombocytopenia (χ2 test = 7.32, p = 0.02). Conclusions Our results suggest that GSTP1 Ile105Val polymorphism could be a predictive biomarker for hematological toxicity, like leukopenia and anemia, but not thrombocytopenia or neutropenia


2021 ◽  
Author(s):  
Lee Webber ◽  
Francesca Fiorentino ◽  
Jonathan Krell ◽  
Consuelo Nohpal de la Rosa

Abstract Background:The standard initial treatment for ovarian cancer is surgery and platinum-based chemotherapy and potentially maintenance therapy with avastin or inhibitors of poly-ADP ribose polymerase (PARP). While a proportion of women are cured by this approach, the vast majority will relapse and become resistant to platinum chemotherapy either initially or on subsequent treatment. There is an unmet need to improve response to treatment and quality of life in these women. TAK228 is a novel therapy that can be added to standard treatment in the participant population and the aim of the DICE trial is to assess its effectiveness. Laboratory and clinical research has shown that these ovarian cancers may respond to the molecular target of a drug such as TAK228, and there have been studies using it in other advanced solid tumours including endometrial cancer. Methods: 124 eligible women will be recruited from participating research sites in the United Kingdom (UK) and Germany. Randomised participants will receive either weekly paclitaxel alone (standard treatment, n=62) or TAK228 plus weekly paclitaxel (n=62) until the cancer significantly worsens, there are significant adverse events or any other protocol-defined stopping criteria. Participants will be monitored for response to treatment (using radiological imaging), adverse events and quality of life during both randomised treatment and subsequent follow up.Discussion:The primary objective/endpoint of the study is to compare the two treatments in terms of progression free survival, or the length of time that each participant is alive without the cancer significantly worsening according to defined assessment criteria. If the addition of TAK228 to weekly paclitaxel chemotherapy is shown to significantly improve this statistically, and adverse events and quality of life are not significantly worse than standard treatment, then TAK228 plus weekly paclitaxel could potentially be taken forward within the context of a larger phase III trial.Trial registration:ClinicalTrials.gov NCT03648489. Registered 27th August 2018.https://clinicaltrials.gov/ct2/show/NCT03648489


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi226-vi226
Author(s):  
Fuhua Lin ◽  
Zhenghe Chen ◽  
Xiangheng Zhang ◽  
Yonggao Mou

Abstract BACKGROUND It is challenging to resect or just biopsy the lesions in the brainstem, due to the essential function of the surfaces and limited space. Neuro-navigation is not always reliable and stereotatic biopsy is infrequently inconclusive due to small or inadequate samples. We want to share our experiences in the application of fluorescein sodium in surgery on patients with brainstem lesion which is contrast enhancing in MRI. METHODS Between January 2017 and June 2021, 5 patients with brainstem lesion underwent fluorescein sodium-guided surgery in neurosurgery department of Sun Yat-sen University Cancer Center. After injection of low dose of sodium fluorescein (3 mg/kg), the lesions with strong fluorescence staining were identified as the target area for biopsy or resection. RESULTS 5 consecutive patients (aged 6–47 years) with brainstem lesions prospectively underwent fluorescein sodium-guided surgery. The lesions were located in pontine in 3 patients and in the medulla in 2 patients. Gross total resection was achieved in 2 patients, and partial resection in the other 3 patients. In all patients, a pathological diagnosis was obtained (4 gliomas and 1 metastasis from non-small cell lung carcinoma) without severe complications, including mild facial or abduct nerve palsy in 3 patients. And all the specimens with strong fluorescence staining sent for pathology were proved to be tumorous. CONCLUSION Fluorescein sodium-guided technique was helpful to locate the lesion in brainstem which was contrast-enhanced in MRI. It was effective and safe to figure out an ideal trajectory to avoid damage of the crucial structures and improve the diagnostic rate.


2019 ◽  
Vol 7 (3) ◽  
pp. 142-143
Author(s):  
Khosro Hekmat

Die vorliegende Studie befasst sich mit dem Einfluss des Alters auf die postoperative Morbidität und Mortalität nach Lungenresektion bei Patienten mit einem nicht kleinzelligen Bronchialkarzinom (non-small cell lung carcinoma, NSCLC) im Stadium I. Am Sloan Kettering Cancer Center (USA) wurden in den Jahren 2000-2011 insgesamt 5371 Patienten einer Lungenresektion unterzogen. 2186 Patienten befanden sich im Stadium I eines NSCLC und wurden in die Studie eingeschlossen. Die multivariate Analyse zeigte, dass die Lungendiffusion (DLCO) ein unabhängiger Prädiktor für die Morbidität, Einjahresmortalität und nicht krebsspezifische Mortalität war. Im Gegensatz dazu war die Einsekundenkapazität (FEV1) ein signifikanter Risikofaktor für die krebsspezifische Mortalität. Die vorliegende Studie zeigt die Relevanz der präoperativen Lungenfunktion mit Bestimmung der DLCO und FEV1. Bei älteren Patienten mit Lungenresektion im Stadium I eines NSCLC ist die nicht krebsspezifische Sterblichkeit in der Frühphase nach der Operation bedeutsam.


Cancer ◽  
2003 ◽  
Vol 97 (9) ◽  
pp. 2242-2247 ◽  
Author(s):  
Vera Hirsh ◽  
Renaud Whittom ◽  
Linda Ofiara ◽  
Pierre Desjardins ◽  
Joseph Ayoub ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7596-7596
Author(s):  
Vijayananda Kundapur ◽  
Tasha Ellchuk ◽  
Shahid Ahmed

7596 Background: Although CRT is a standard therapy for prevention and treatment of brain metastases (BM) in patients with SCLC, neurocognitive impairment (NI) following therapeutic whole brain radiation treatment (WBRT) or prophylactic cranial irradiation (PCI) is a major problem and can cause impairment in quality of life. A RTOG study is assessing various outcomes by avoiding the hippocampus (AH) during WBRT in different malignancies. The estimated risk of hippocampal avoidance region metastases (HM) in patients with SCLC before & after WBRT/PCI is not known. AH during CRT may delay the onset of NI in such patients. Our study aims to determine risk of HM in patients with SCLC and to assess clinical factors correlate with it. Methods: A patients cohort of SCLC diagnosed and treated at the Saskatoon Cancer Center between 2005 and 2012 were followed. All MRI and/or CT scans were independently reviewed by a neuroradiologist. HM was defined as BM within 5 mm of hippocampus. Binary Logistic regression analysis was done to assess correlation between various clinical variables and HM using SPSS. Results: 162 patients with SCLC were identified, 60 (37%) have developed BM. The preliminary data of 39/60 patients is presented here. All 39 patients received CRT and 17 patients received upfront chemotherapy. Their median age was 63 yrs (range: 41-82) & M:F was 22:17. 30 (77%) had extensive stage SCLC and 30 (77%) had de novo BM before CRT. A total 198 (range: 1-33) BM were identified among these patients with a mean BM of 6.6 per patient. 4 (13.3%) of 30 patients had HM involvement with mean BM of 1.3 per patient. Median follow up was 13.5 months (range: 1-69). Post-CRT 13 (33%) of 39 patients (4 PCI, 9 WBRT) developed central nervous system (CNS) progression. None of 13 patients with CNS failure following CRT developed HM. Overall 4 (10.2%) of 39 patients developed HM. No clinical factors significantly correlated with HM. Conclusions: The preliminary result revealed that overall incidence of HM before and after WBRT/PCI is low. AH in such patients may consider during CRT to avoid NI. The study is ongoing and final analysis will be presented.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13001-13001 ◽  
Author(s):  
D. Glenn ◽  
F. Ueland ◽  
A. Bicher ◽  
D. Dizon ◽  
M. Gold ◽  
...  

13001 Background: Pertuzumab (P), a humanized HER2 antibody, represents a new class of targeted agents called HER dimerization inhibitors (HDIs). P inhibits dimerization of HER2 with EGFR, HER3 and HER4, and subsequently inhibits signaling through MAP and PI3 kinases. Single agent P has demonstrated clinical benefit in advanced OC (ASCO 2005 abstract #5051). Methods: 40 pts with platinum-resistant OC (progressed within 6 months of receiving a platinum-based chemotherapy) were enrolled in this 1:1 randomized, double blind, placebo controlled trial of gemcitabine with or without P. Gemcitabine was administered IV on day 1 and 8 at 800 mg/m2 of a 21 day cycle. Blinded placebo or 420 mg P was administered IV on day 1. Gemcitabine was dose reduced for neutropenia or thrombocytopenia. P was not dose reduced. Results: 40 pts have been enrolled and treated with at least 1 cycle of gemcitabine in combination with blinded study drug. The median age was 58.5 (range 18–82); 26 had PS ECOG 0, 13 ECOG 1, 1 ECOG 2. The most common grade 3/4 events were neutropenia in 7 pts (17.5%), thrombocytopenia in 6 pts (15%), small bowel obstruction in 4 pts (10%), constipation in 3 pts (7.5%) and elevated ALT in 3 pts (7.4%). There was one grade 3 diarrhea, but no grade 3 or 4 rash. There were 4 serious adverse events (SAEs) attributed to study drug. These were a pleural effusion, thrombocytopenia, febrile neutropenia, and a deep vein thrombosis. Nine pts required one or two dose reductions of gemcitabine for hematological toxicity. Of 29 pts with post-baseline echo or MUGA values obtained, no pt had LVEF drop to <50%. The adverse events evaluated after 40 pts did not meet the prespecified criteria to call for an independent safety monitoring board evaluation of unblinded data. Conclusions: Preliminary safety data indicate that pertuzumab or placebo combined with gemcitabine is well tolerated with no unexpected additive toxicity. The nature and frequency of the adverse events are similar to what has been observed with either single agent gemcitabine or P. Updated data will be presented at ASCO. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20646-e20646
Author(s):  
Prantesh Jain ◽  
Monica Khunger ◽  
Vinay Pasupuleti ◽  
Adrian V Hernandez ◽  
Vamsidhar Velcheti

e20646 Background: Drugs targeting the PD-1/PD-L1 pathway show significant clinical activity in non-small cell lung carcinoma (NSCLC). Nivolumab, pembrolizumab and atezolizumab are currently approved for NSCLC patients who have progressed while on platinum-based chemotherapy. Recently, pembrolizumab received FDA approval for treatment naive NSCLC patients with tumor PD-L1 expression of ≥50%. However, there is relative lack of data on comparative efficacy of these drugs in the chemotherapy naive versus post-chemotherapy setting. In the current meta-analysis we compare the efficacy and toxicity of these drugs in chemotherapy naïve patients with those who receive them as subsequent therapy (after previous chemotherapy). Methods: A systematic search of electronic databases (PubMed-Medline, EMBASE, Scopus) and major conference proceedings was done for all clinical trials using PD1/PD-L1 inhibitors. Objective response rates (ORR) for patients determined to have positive tumor PD-L1 expression (Tumor Proportion Score ≥1%) from all phase I-III trials investigating nivolumab, pembrolizumab, atezolimumab, durvalumab and avelumab for NSCLC were collected. Only single agent PD-1/PDL-1 inhibitor trials were included. The ORR across trials was combined using DerSimonian-Laird random effects models. Higgins’ I2 statistic was used to assess heterogeneity. Results: 19 trials (7 with treatment naïve patients [n = 651]; 14 with chemotherapy treated patients [n = 2205]; 2 with separate treatment naïve and previously treated arms) were included. Treatment naïve patients were found to have statistically significant higher efficacy [ORR 28.27%(95% CI 20.70-36.52)] than those who received these drugs as subsequent therapy [ORR 20.13% (95%CI 17.53-22.85) (p = 0.02). Treatment naive patients had statistically significant higher rates of all grade pneumonitis as comapred to previously treated patients (4.9, 95%CI 3.4-6.7 vs 3.0 95% CI 2.0-4.1). Conclusions: PD1/PDL1 therapy for advanced NSCLC has a significantly improved efficacy (based on ORR) when used in treatment naïve patients as compared to its use in patients who have been previously treated with chemotherapy.


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