Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer

PURPOSE To evaluate the safety and efficacy of gemcitabine and cisplatin in combination with the immune checkpoint inhibitor pembrolizumab as neoadjuvant therapy before radical cystectomy (RC) in muscle-invasive bladder cancer. METHODS Patients with clinical T2-4aN0/XM0 muscle-invasive bladder cancer eligible for RC were enrolled. The initial six patients received lead-in pembrolizumab 200 mg once 2 weeks prior to pembrolizumab 200 mg once on day 1, cisplatin 70 mg/m2 once on day 1, and gemcitabine 1,000 mg/m2 once on days 1 and 8 every 21 days for four cycles. This schedule was discontinued for toxicity and subsequent patients received cisplatin 35 mg/m2 once on days 1 and 8 without lead-in pembrolizumab. The primary end point was pathologic downstaging (< pT2N0) with null and alternative hypothesis rates of 35% and 55%, respectively. Secondary end points were toxicity including patient-reported outcomes, complete pathologic response (pT0N0), event-free survival, and overall survival. Association of pathologic downstaging with programmed cell death ligand 1 staining was explored. RESULTS Thirty-nine patients were enrolled between June 2016 and March 2020 (72% cT2, 23% cT3, and 5% cT4a). Patients received a median of four cycles of therapy. All patients underwent RC except one who declined. Twenty-two of 39 patients (56% [95% CI, 40 to 72]) achieved < pT2N0 and 14 of 39 (36% [95% CI, 21 to 53]) achieved pT0N0. Most common adverse events (AEs) of any grade were thrombocytopenia (74%), anemia (69%), neutropenia (67%), and hypomagnesemia (67%). One patient had new-onset type 1 diabetes mellitus with ketoacidosis related to pembrolizumab and no patients required steroids for immune-related AEs. Clinicians consistently under-reported AEs when compared with patients. CONCLUSION Neoadjuvant gemcitabine and cisplatin plus pembrolizumab met its primary end point for improved pathologic downstaging and was generally safe. A global study of perioperative chemotherapy plus pembrolizumab or placebo is ongoing.

EVALUATION OF THE ROLE OF GEMCITABINE AND ERLOTINIB IN STAGE IIIB AND STAGE IV NSCLC ADENOCARCINOMA OF LUNG AS A FIRST LINE CHEMOTHERAPY REGIMEN AND ASSESSING THE ACUTE TOXICITY, OVERALL SURVIVAL AND PROGRESSION FREE SURVIVAL RESPECTIVELY.

INTRODUCTION: 2 nd rd According to Globocan 2020 lung cancer is 2 most common malignancy in males and 3 most common in the females. st Previous studies have showed EGFR-tyrosine-kinase inhibitors erlotinib and getinib efcacy as 1 line treatment for patients with activating EGFR mutations. Also, Gemcitabine is drug of choice in inoperable and locally advanced metastatic NSCLC. With the purpose study was undertaken to evaluate the role of gemcitabine and erlotinib in stage IIIB and stage IV NSCLC adenocarcinoma of lung MATERIAL AND METHOD: 2 35 Patients with stage IIIB and IV fullling criteria were given Inj. Gemcitabine 1 gm/m D1 and D8 IV & Tab erlotinib 150 mg PO daily repeated every 21 days, 6 cycles. Post 6 cycles of chemotherapy tab erlotinib 150 mg given till disease progression. Tumor response assessed by RECIST 1.1. Toxicity assessed by CTCAE version 5.0. RESULT: Adrenal metastasis was most common followed by lung, bone, malignant pleural effusion and liver metastasis. a median follows up in this study was 33 weeks. Toxicities noted were anemia, thrombocytopenia, febrile neutropenia, GI toxicities and rash. In post 3 cycles of chemotherapy, out of 35 patients,62.86 % were having partial response for primary and 34.29 % (n=12) for metastatic lesions. In post 6 cycles of chemotherapy there was a reduction in the partial response patients and a steep rise in stable disease patients. In Post 12 weeks of 6 cycles of chemotherapy more patients having a progressive disease, very little, 5.71 % having PR and 25.71 % were having a stable disease. DISCUSSION: The median PFS and median OS was 4.1 and 5.6 months respectively whereas Grade 3 toxicity was also seen in gemcitabine plus erlotinib arm. INTACT 1 trial-getinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase III trial showed that getinib in combination with gemcitabine and cisplatin in chemotherapy-naive patients with advanced NSCLC did not have improved efcacy over gemcitabine and cisplatin alone. The median overall survival was 18.3 months and the median PFS was 7.6 months, in our study it come out to be 8.25 months and 4.5 months respectively. Also noted Grade 3 febrile neutropenia, anemia, thrombocytopenia, vomiting & diarrhea same as our study. CONCLUSION: Standard treatment for patients with an activating EGFR mutation is rst-line single-agent EGFR-tyrosine kinase inhibitor and combination chemotherapy such as gemcitabine plus erlotinib is improving survival

Gemcitabine-Related Atrial Fibrillation: A Case Report and Review of the Literature

: Gemcitabine is a commonly used antimetabolite that has been effective in a broad spectrum of tumors so far. The main grade three and four known toxicity of this drug is myelosuppression. Cardiac adverse events have rarely been reported and gemcitabine-induced atrial-fibrillation (AF) has been described in only five previous cases so far. Here we report the 6th case of gemcitabine-related AF. A 68-year-old man diagnosed with metastatic nasopharyngeal cancer was referred to our oncology department. He started first line chemotherapy with gemcitabine and cisplatin. He presented poorly tolerated atrial fibrillation related to gemcitabine infusion that lasted for six days. The treatment was then withdrawn and the patient received best supportive care. We conclude that Medical oncologists and cardiologists should be aware of such toxicities of gemcitabine, especially in the elderly who seem to be at a higher risk of such adverse events and which may dictate discontinuation of the drug.

Successful Response of Pembrolizumab Rechallenge after Radiotherapy for a Patient with Bladder Cancer of Nonresponse of Pembrolizumab First Challenge

We report a patient with advanced bladder cancer in which the primary lesion and metastatic site disappeared following the pembrolizumab therapy rechallenge after radiotherapy for bladder cancer lesion of nonresponse of pembrolizumab first challenge. A 76-year-old man with advanced bladder cancer received three courses of the chemotherapy with gemcitabine and cisplatin combination; however, the chemotherapy was stopped because of adverse events. The patient started pembrolizumab therapy; however, the effect was not observed. Radiation therapy was given to the primary lesion and pelvic lymph node metastases for the purpose of local control of the lesions. Because the primary lesion was regrowth and para-aortic lymph node metastasis appeared, pembrolizumab therapy was resumed. Thereafter, the primary lesion and metastatic site disappeared.

First Report of Oncological Outcome and Prognostic Analysis in a First-Line Setting of Short Hydration Gemcitabine and Cisplatin Chemotherapy for Patients with Metastatic Urothelial Carcinoma

<b><i>Objectives:</i></b> The aim of the study was to examine the effectiveness of a modified-short hydration gemcitabine and cisplatin (m-shGC) regimen for patients with metastatic urothelial carcinoma (mUC) and to assess the efficacy of a geriatric nutritional risk index (GNRI) with regard to prognosis. <b><i>Patients and Methods:</i></b> From January 2016 to July 2020, 68 patients with mUC underwent first-line m-shGC therapy with 70 mg/m² cisplatin and 1,000 mg/m² gemcitabine (days 1, 8, and 15), with 2,050 mL fluid replaced on the first day of each 28-day cycle. Prior to the start of treatment, the serum neutrophil-to-lymphocyte ratio (NLR), and levels of albumin and C-reactive protein (CRP) in serum, as well as body heights and weights were measured. Patients were grouped according to GNRI &#x3c;92 (low) or ≥92 (high). The analysis of data was done retrospectively. <b><i>Results:</i></b> Median follow-up was found to be 12.9 (range 1.7–50.2) months and the objective response rate (ORR) was 54.4% after m-shGC treatment. The ORR was significantly different when high and low-GNRI groups were compared (ORR: 28.0 vs. 69.8% in low- vs. high-GNRI groups). Median overall survival (OS) was calculated as 8.6 (95% confidence interval [CI]: 5.4–21.3) and 34.5 (95% CI: 20.5–NA) months for low- and high-GNRI groups, respectively (<i>p</i> &#x3c; 0.0001). Unlike for NLR and CRP, univariate and multivariate analyses revealed that low GNRI and visceral metastases were significant prognostic factors for short OS. <b><i>Conclusions:</i></b> First-line m-shGC showed a survival benefit for mUC, with GNRI a useful prognostic biomarker.