Reduced frequency dosing of osimertinib in EGFR-mutant non-small cell lung carcinoma: real world data.

Introduction: Osimertinib is more efficacious and as safe as first-generation epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibitors. However, osimertinib is not affordable for most patients in developing nations. Moreover, the minimum biologically effective dose of osimertinib may be less than the approved dose. Materials and methods: This was a retrospective observational multicentric study aimed to describe the efficacy (objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS)) and toxicity of osimertinib 80 mg orally administered less frequently than daily (ranging from every other day to once-a-week) in patients with EGFR-mutated non-small cell lung cancer. Results: Between January 2021 and August 2023, we enrolled 22 patients. Six received osimertinib 80 mg once-a-week, nine received 80 mg once-in-3-days and seven received 80 mg on alternate days. Responses included 0 complete responses, 7 (31.8%) partial responses, 9 (40.9%) stable disease and 5 (22.7%) progressive disease. ORR was 31.8%, and DCR was 72.7%. Median PFS was 9.2 months (95% confidence interval (CI) 2.9-15.7), and median OS was 17.8 months (95% CI, 3.2-32.6). In patients who received reduced frequency osimertinib in the second line and beyond, the ORR was 29.4%, DCR was 70.5%, median PFS was 5.9 months (95% CI, 1.1-10.6) and median OS was 17.6 months (95% CI, 2.9-32.2). Grade 3 and higher toxicities were noted in 8 (36.3%) patients. Conclusion: Less frequent dosing of osimertinib may be a valid treatment option, especially in the second line and beyond setting in patients who cannot afford full dose daily osimertinib. This may provide an additional treatment option with a similar toxicity profile as that of standard dose osimertinib.

Results of Phase III Randomized Trial for Use of Docetaxel as a Radiosensitizer in Patients With Head and Neck Cancer, Unsuitable for Cisplatin-Based Chemoradiation.

PURPOSE: There is a lack of published literature on systemic therapeutic options in cisplatin-ineligible patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) undergoing chemoradiation. Docetaxel was assessed as a radiosensitizer in this situation. METHODS: This was a randomized phase II/III study. Adult patients (age ≥ 18 years) with LAHNSCC planned for chemoradiation and an Eastern Cooperative Oncology Group performance status of 0-2 and who were cisplatin-ineligible were randomly assigned in 1:1 to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS). RESULTS: The study recruited 356 patients between July 2017 and May 2021. The 2-year DFS was 30.3% (95% CI, 23.6 to 37.4) versus 42% (95% CI, 34.6 to 49.2) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.673; 95% CI, 0.521 to 0.868; P value = .002). The corresponding median overall survival (OS) was 15.3 months (95% CI, 13.1 to 22.0) and 25.5 months (95% CI, 17.6 to 32.5), respectively (log-rank P value = .035). The 2-year OS was 41.7% (95% CI, 34.1 to 49.1) versus 50.8% (95% CI, 43.1 to 58.1) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.747; 95% CI, 0.569 to 0.980; P value = .035). There was a higher incidence of grade 3 or above mucositis (22.2% v 49.7%; P < .001), odynophagia (33.5% v 52.5%; P < .001), and dysphagia (33% v 49.7%; P = .002) with the addition of docetaxel. CONCLUSION: The addition of docetaxel to radiation improved DFS and OS in cisplatin-ineligible patients with LAHNSCC.[Media: see text].

Neuroleptic malignant-like syndrome causing thrombocytopaenia: a rare association.

Neuroleptic malignant-like syndrome is a rare but potentially fatal complication of sudden withdrawal of dopaminergic drugs. Clinical features are similar to that of neuroleptic malignant syndrome (NMS) like hyperthermia, autonomic dysfunction, altered sensorium, muscle rigidity; but instead of history of neuroleptic use, there is history of withdrawal of dopaminergic drugs. Laboratory examination generally show elevated creatine phosphokinase levels and may show elevated total leucocyte count. Thrombocytopaenia has been very rarely reported with NMS but it has not been reported with NM-like syndrome. Here, we discuss a case of Parkinson's disease which presented with typical clinical features and risk factors of NM-like syndrome associated with thrombocytopaenia and type 1 respiratory failure. He was treated with bromocriptine and supportive care. Thrombocytopaenia and respiratory failure resolved with above treatment. The patient improved clinically and was successfully discharged on day 12 of admission.

CRAB Manifestations in a Middle-Aged Female: A Diagnostic Dilemma.

A 56 year old lady, presented to our institute with six months history of low grade fever, generalized weakness, decreased food intake and fluctuating sensorium. Initial investigations revealed hypercalcemia, renal dysfunction and anemia. Initial working diagnosis of likely underlying hematological malignancy such as lymphoma or multiple myeloma (MM) was kept after hyperparathyroidism was ruled out. Her skeletal survey revealed lytic lesions in the skull, bone marrow aspirate showed 12% plasma cells and beta-two microglobulin level was markedly elevated. However, the criterion for MM was not fully satisfied. In view of persistent altered sensorium, MRI brain was done which suggested the diagnosis of disseminated tuberculosis and was further confirmed through MR spectroscopy, bone marrow biopsy (showing granulomas) and whole body PET. She was started on anti-tubercular therapy along with steroids with marked response within a week. We describe the details of this interesting case through a systematic approach to the various features.

Late Presentation of Post Diphtheritic Myocarditis in a 15-year Male.

A 15-year old male patient presented to us with dyspnoea for four days. He had a history of fever, pseudo-membranous tonsillitis and cervical adenopathy twenty-five days prior to the presentation. On examination and laboratory investigations, he had features suggestive of myocarditis with biventricular failure. There was no reliable history of immunisation and he had a positive history of contact. He was planned for anti-diphtheria toxin but before the anti-toxin could be initiated, the patient succumbed to refractory cardiogenic shock. This was a rare case of late onset diphtheritic myocarditis in an unimmunised adult. With the advent of universal immunisation, there has been a significant decline in the incidence but there is still some road to cover.