Patients treated with platinum-based chemotherapy frequently experience neurotoxic symptoms, which may lead to premature discontinuation of therapy. Despite discontinuation of platinum drugs, these symptoms can persist over a long period of time. Cisplatin and oxaliplatin, among all platinum drugs, have significant neurotoxic potential. A distal dose-dependent symmetrical sensory neuropathy is the most common presentation of platinum neurotoxicity. DNA damage-induced apoptosis of dorsal root ganglion (DRG) neurons seems to be the principal cause of neurological symptoms. However, DRG injury alone cannot explain some unique symptoms such as cold-aggravated burning pain affecting distal extremities that is observed with oxaliplatin administration. In this article, we briefly reviewed potential mechanisms for the development of platinum drugs-associated neurological manifestations.
Human epidermal growth factor receptor 2 (HER2) signaling pathway activation has been identified as a contributor to de novo or acquired resistance to epidermal growth factor receptor (EGFR) inhibitors in a small subset of patients with metastatic colorectal cancer (mCRC). Dual anti-HER2-targeted treatment exhibits strong antitumor activity in preclinical models of HER2-positive mCRC, supporting its testing in clinical trials. The HERACLES trial at four Italian academic cancer centers has confirmed the effectiveness of dual blockage of HER2 with trastuzumab plus lapatinib in patients with heavily pretreated HER2-positive mCRC, refractory to the anti-EGFR antibodies cetuximab or panitumumab. Here, we reviewed the preclinical studies exploring the role of HER2 signaling in the development of anti-EGFR therapy resistance and discussed the status of clinical trials assessing the activity of HER2 inhibitors in this setting.
The treatment of metastatic colorectal cancer (mCRC) harboring BRAF V600 mutations is challenging. These tumors are often refractory to standard treatment. Therefore, the patients may exhibit rapid clinical deterioration, depriving them of the chance to receive salvage therapy. In newly diagnosed patients with good performance status, the administration of an intensive chemotherapy regimen like FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) along with the antiangiogenic agent bevacizumab can modify this aggressive behavior of the disease and improve patient clinical outcomes. The recently published results of the BEACON (Binimetinib, Encorafenib, and Cetuximab Combined to Treat BRAF-Mutant Colorectal Cancer) study demonstrated that a combination therapy consisting of BRAF, epidermal growth factor receptor, and mitogen-activated protein kinase kinase inhibitors could be a useful second-or third-line alternative. This review summarizes the current treatment strategies for BRAF -mutant mCRC.
BackgroundIn non-small cell lung cancer (NSCLC), immunotherapy is a treatment option in patients without targetable mutations in second and later lines. Nevertheless, there is no validated test that can predict immunotherapy response. Material and MethodsOur study aimed to investigate the effect of radiotherapy (RT) on survival in patients with NSCLC receiving immunotherapy after first-line chemotherapy. Twenty-five patients diagnosed with NSCLC and received immunotherapy after at least one previous chemotherapy line were included in our study. ResultsThe median age of the patients was 61.7 (26.6-81.2) years. 19 (76%) patients were male. 11 (44%) of the patients had received immunotherapy in the second-line and 14 (66%) in ≥3 lines. Patients had received a median of 5 cycles (1-27) of immunotherapy. RT to immunotherapy interval was 6.4 months (1.0-11.8). Partial response was observed in 12 patients, stable disease in 8 patients, progression in 1 patient, and hyperprogression in 4 patients. Median progression-free survival (PFS) was 4.4 months (95% CI; 3.2-5.6), and median overall survival (OS) was 16.4 months (95% CI; 5.6-27.3). 14 (56%) of the patients had received RT. RT was administered to 12 patients before immunotherapy, and two patients received RT to bones during immunotherapy. The patients who received RT had statistically longer PFS (4.9 vs 3.9 months, p=0.012) and OS (18.7 vs 7.3 months, p=0.023) comparing those without RT. Conclusions Our findings showed that RT significantly improved the survival in patients who received immunotherapy, pointing that RT may have an influential role in immunotherapy response.
Introduction Hyperprogression is a specific type of response seen with immunotherapy that is observed in all malignancies with a frequency of 9% - 29%, characterized by a rapid increase in tumor burden. Many possible related factors and possible markers have been evaluated but a clinical or laboratory parameter associated with hyperprogression has not yet been established. For renal cell carcinoma, hypercalcemia is known to be a poor prognostic factor but it has not been linked to hyperprogression. Case report We retrospectively evaluated 52 patients diagnosed with renal cell carcinoma who had nivolumab treatment in any line. 3 of 9 patients who had hyperprogression were noticed to have hypercalcemia preceding hyperprogression. Here we present those 3 cases who developed hypercalcemia after nivolumab and had hyperprogression at follow-up. Management and outcome All cases had less than 4 courses of nivolumab and showed hyperprogression in assessment. Nivolumab was discontinued. However, patients’ survival was extremely poor, as expected. Discussion The development of hypercalcemia may help predict hyperprogression in patients with renal cell carcinoma who receive immunotherapy. In such cases, early evaluation of progression and cessation of nivolumab may be considered.
Introduction: Osimertinib, an irreversible third-generation EGFR-TKI, is the standard of care for second-line treatment of T790M-mutant advanced NSCLC patients whose progressed after first-line EGFR-TKI therapy. In this multicenter study, we aimed to determine the real-life efficacy and safety of Osimertinib in pretreated advanced NSCLC patients with T790M mutation.Materials and Methods: This retrospective trial included advanced T790M-mutant pretreated NSCLC patients who received Osimertinib from 24 different centers in Turkey. Primary endpoint was time-to-treatment discontinuation (TTD). Secondary endpoints were objective response rate (ORR), overall survival (OS), and safety.Results: Of 163 patients 68.7% had EGFR exon 19 deletion and 22.7% had exon 21 L858R mutation. Osimertinib was given as second-line treatment in 96 patients (58.9%) and third-line in 48 patients (29.4%). After median of 13 months disease follow-up, median TTD was 21.6 months with an 82.2% ORR. Estimated median OS was 32.1 months. Grade 3-4 adverse events were seen in 11.7% of the patients. Conclusion: Osimertinib is a highly effective option in second or third-line treatment of NSCLC patients with T790M mutation, with a favorable safety profile.
Introduction: Osimertinib, an irreversible third-generation EGFR-TKI, is the standard of care for second-line treatment of T790M-mutant advanced NSCLC patients whose progressed after rst-line EGFR-TKI therapy. In this multicenter study, we aimed to determine the real-life e cacy and safety of Osimertinib in pretreated advanced NSCLC patients with T790M mutation.Materials and Methods: This retrospective trial included advanced T790M-mutant pretreated NSCLC patients who received Osimertinib from 24 different centers in Turkey. Primary endpoint was time-totreatment discontinuation (TTD). Secondary endpoints were objective response rate (ORR), overall survival (OS), and safety.Results: Of 163 patients 68.7% had EGFR exon 19 deletion and 22.7% had exon 21 L858R mutation. Osimertinib was given as second-line treatment in 96 patients (58.9%) and third-line in 48 patients (29.4%). After median of 13 months disease follow-up, median TTD was 21.6 months with an 82.2% ORR. Estimated median OS was 32.1 months. Grade 3-4 adverse events were seen in 11.7% of the patients. Conclusion:Osimertinib is a highly effective option in second or third-line treatment of NSCLC patients with T790M mutation, with a favorable safety pro le.
ÖZETEndometrium kanseri (EK) gelişmiş ülkelerde en sık görülen jinekolojik kanserdir. Obezite en önemli risk faktörü olarak kabul edilmektedir. Endometrium kanserleri içerisinde en sık görülen alt tip endometrioid endometrial karsinomdur (EEK). Çalışmamızda metastatik EEK hastalarının demografik ve klinikopatolojik özelliklerini, kullanılan tedavi yöntemlerinin sağ kalıma etkisini incelemeyi amaçladık. Hastaların medyan yaşı 58 (39,9) idi. On altı hastanın hastaneye başvuru şikayeti vajinal kanamaydı. Medyan takip süresi 43 (0,2-104,3) aydı. Hastaların medyan progresyonsuz sağkalım (PS) süresi 39,9 ay (%95 güven aralığı (GA): 35,0-79,1), medyan genel sağkalım (GS) süresi 59,1 ay (%95 GA: 39,1-80,8) saptandı. Kemoradyoterapi alan hastaların PS ve GS süresi sadece kemoterapi ile tedavi edilen hastalara göre istatistiksel anlamlı olarak daha uzundu (log-rank testi, PS için p=0,012, GS için p=0,015). Çalışmamız metastatik evrede seçilmiş hasta grubunda kemoradyoterapinin tercih edilebileceğini desteklemektedir.
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