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Importance: The role of olanzapine has not been adequately evaluated in moderately emetogenic chemotherapy (MEC) regimens with or without neurokinin-1 receptor antagonists. Objective: To evaluate whether addition of olanzapine to an MEC regimen reduces nausea, vomiting, and use of nausea rescue medications among patients with solid malignant tumors. Design, Setting, and Participants: This multicenter, open-label phase 3 randomized clinical trial included patients aged 18 years or older with solid malignant tumors who were receiving oxaliplatin-, carboplatin-, or irinotecan-based chemotherapy. The trial was conducted at 3 institutes in India from March 26, 2019, to August 26, 2023; the final cutoff date for analysis was September 10, 2023. Exposure: Patients were randomized 1:1 to dexamethasone, aprepitant, and palonosetron with olanzapine (experimental group) or without olanzapine (observation group). The experimental group received 10 mg of olanzapine orally once at night on days 1 through 3 of the chemotherapy regimen. Main Outcomes and Measures: The primary end point was complete response (CR), defined as the proportion of patients with no vomiting, no significant nausea (scored as <5 on a visual analog scale of 1 to 100), and no use of rescue medications for nausea. Secondary end points included the proportion of patients experiencing nausea and chemotherapy-induced nausea and vomiting (CINV), receiving rescue medications, and experiencing adverse events. Results: A total of 560 patients (259 [64%] male; median age, 51 years [range, 19-80 years]) were randomized. The analysis included 544 patients with evaluable data (274 assigned to olanzapine and 270 to observation). Baseline characteristics were evenly matched between the 2 groups. The proportion of patients with CR was significantly greater in the group with (248 [91%]) than without (222 [82%]) olanzapine in the overall 120-hour treatment period (P = .005). Likewise, there were significant differences between the olanzapine and observation groups for nausea control (264 [96%] vs 234 [87%]; P < .001) and CINV (262 [96%] vs 245 [91%]; P = .02) during the overall assessment period, and the proportion of patients receiving rescue medications significantly increased in the observation group (30 [11%]) compared with the olanzapine group (11 [4%]) (P = .001). Grade 1 somnolence was reported by 27 patients (10%) following administration of chemotherapy and olanzapine and by no patients in the observation group. Conclusions and Relevance: In this randomized clinical trial, the addition of olanzapine significantly improved CR rates as well as nausea and vomiting prevention rates in chemotherapy-naive patients who were receiving MEC regimens containing oxaliplatin, carboplatin, or irinotecan. These findings suggest that use of olanzapine should be considered as one of the standards of care in these chemotherapy regimens. Trial Registration: Clinical Trials Registry-India (CTRI) Identifier: CTRI/2018/12/016643.
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Antieméticos , Náusea , Neoplasias , Olanzapina , Vómitos , Humanos , Olanzapina/uso terapéutico , Antieméticos/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Vómitos/inducido químicamente , Vómitos/prevención & control , Náusea/inducido químicamente , Náusea/prevención & control , Adulto , Neoplasias/tratamiento farmacológico , Anciano , Aprepitant/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Dexametasona/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Palonosetrón/uso terapéutico , IndiaRESUMEN
BACKGROUND: We evaluated whether the addition of docetaxel (D) to a combination comprising 5-fluorouracil/leucovorin (5-FU/LV) or capecitabine (C) plus oxaliplatin (O) (DOF/DOX) improved overall survival (OS) compared with 6 months of 5-fluorouracil (5-FU) or capecitabine in combination with oxaliplatin (FOLFOX/CAPOX) alone in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas (G/GEJ). METHODS: This study was an investigator-initiated, open-label, multi-institutional, randomized phase III trial in adult patients with HER2-negative advanced G/GEJs. The primary endpoint of the study was a comparison of median OS by Kaplan-Meier method. Next-generation sequencing was performed on tissue. RESULTS: Of the 324 patients randomly assigned between July 2020 and November 2022, 305 patients were evaluable for analysis (FOLFOX/CAPOX: 156; DOF/DOX: 149). With a median follow-up time of 19.2 months (95% Confidence Interval [CI] = 16.5 months to 21.9 months) for the entire cohort, the median OS was 10.1 months (95% CI = 9.2 to 10.9) for FOLFOX/CAPOX and 8.9 months (95% CI = 7.3 to 10.5) for DOF/DOX, and this difference was not statistically significant (P = .70). An increased proportion of grade 3 or grade 4 neutropenia (21% vs 3%; P < .001) and grade 2/3 neuropathy (17% vs 7%; P = .005) was seen in patients receiving DOF/DOX. Genomic profiling revealed a low incidence of microsatellite instability (1%) and a high incidence of BRCA1 (8.4%) and BRCA2 (7.5%) somatic alterations. CONCLUSION: FOLFOX or CAPOX chemotherapy for 6 months remains one of the standards of care in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas, with no additional survival benefit seen with the addition of docetaxel. Genomic profiling of patients revealed a higher than previously known incidence of somatic BRCA alterations, which requires further evaluation.CTRI (Clinical Trial Registry of India: CTRI/2020/03/023944).
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Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Docetaxel , Unión Esofagogástrica , Fluorouracilo , Leucovorina , Oxaliplatino , Receptor ErbB-2 , Neoplasias Gástricas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidad , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Persona de Mediana Edad , Femenino , Capecitabina/administración & dosificación , Capecitabina/efectos adversos , Docetaxel/administración & dosificación , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Anciano , Receptor ErbB-2/genética , Oxaliplatino/administración & dosificación , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adulto , Estimación de Kaplan-Meier , Compuestos Organoplatinos/administración & dosificación , Inestabilidad de Microsatélites , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patologíaRESUMEN
OBJECTIVES: With sensitive imaging for breast cancer, the question arises whether present-day oncologists treat dOMBC with palliative systemic therapy (ST), which, a few years earlier, would have been treated with curative intent. We retrospectively analyzed outcomes of dOMBC treated with curative intent using a combination of surgery, metastasis-directed radiotherapy (RT), and adjuvant/neoadjuvant ST and have also explored the possible role of total lesional glycolysis of metastases and p53 immunohistochemistry in predicting outcomes. METHODS: Data were collected from a prospectively maintained database using electronic medical records and Radiation Oncology Information System. In the study, dOMBC was defined as up to 3 metastatic sites, all amenable to treatment with ablative RT and primary and axillary disease amenable to curative surgery. Patients were treated with surgery, ST, and RT. RESULTS: Patients underwent either breast conservation surgery or modified radical mastectomy. Patients were treated with 6 to 8 cycles of chemotherapy in the neoadjuvant and/or adjuvant setting. Hormone receptor-positive patients received either tamoxifen or aromatase inhibitors. Trastuzumab was offered to Her-2-neu receptor-positive patients. RT included locoregional RT and metastases-directed ablative body RT. The median progression-free survival was 39 months (95% CI: -28.7 to 50.1 mo). Two and 3 year estimated disease-free survival (DFS) was 79% and 60.5%, respectively. The median overall survival was not reached. The estimated 3-year overall survival was 87.3%. Total lesional glycolysis of metastases score and p53 status did not affect DFS. CONCLUSION: Combination treatment of surgery, metastases-directed ablative RT, and ST may provide prolonged DFS in dOMBC.
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BACKGROUND: Breast lymphomas are a rare group of malignancies that are further subdivided into primary and secondary. AIMS: To study the pathological and clinical course of breast lymphomas. MATERIALS AND METHODS: This is a retrospective analysis of patients treated at our institute over a period of 4.5 years from September 2018 to February 2023. The details of all the patients diagnosed with breast lymphoma were reviewed and analysed for the histomorphological, immunohistochemical, clinical, and treatment details. Appropriate statistical analysis including Kaplan-Meier methods was used. RESULTS: Out of 11 cases of breast lymphoma, five were primary and six were secondary. It was seen predominantly in females (82%) and the age range was 31 to 73 years. Diffuse large B cell lymphoma (DLBCL) was the predominant morphology (73%), along with single rare cases of ALK-negative anaplastic large cell lymphoma, Burkitt lymphoma, and small lymphocytic lymphoma. The treatment details were analyzed for 7 patients. The median follow-up was 28 months. Rituximab along with CHOP regimen or its variants was commonly used as first-line treatment with initial response rates of 71%. The median progression-free survival was 5 months. The median overall survival was 15 months. CONCLUSION: Lymphomas of the breast are rare but it is crucial to differentiate them from the commoner breast carcinomas as the treatment and prognosis vary vastly.
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Lakhan KasyapIntroduction Gallbladder cancer (GBC) is the 20th most common cancer in India with a crude incidence rate of 2.3 per 100,000 persons. Of note, it is relatively common in states which fall in the Gangetic plains. Patients often present in the advanced stage and have an unfavorable prognosis. Materials and Methods From January to June 2021, 170 treatment-naive GBC (adenocarcinoma) patients who were registered at a tertiary care cancer center in North India, were included. Data were extracted from electronic medical records and was analyzed with SPSS. Results Median age was 56 years (range 32-77 years) and 65.5% ( n = 112) were female. Incidental GBC was found in 20% patient ( n = 34). Majority of patients (79.4%, n = 135) had preserved performance status. Advanced GBC was present in 85.8% ( n = 146) patients (locally advanced = 37.0% and metastatic = 48.8%). Biliary drainage procedure was performed in 24% of patients (68% of patients with obstructive jaundice). More than half of patients (53.5%) were lost to follow-up without any treatment. There were 33 patients (19.4%) who underwent surgery and 20 of them received neoadjuvant chemotherapy. Adjuvant chemotherapy and adjuvant radiotherapy were received by 13 and 2 patients, respectively. Palliative chemotherapy was administered to 46 patients. The most common chemotherapy regimen was gemcitabine-cisplatin. At a median follow-up of 1.7 months (95% confidence interval, 1-2.4 months), 42 patients (24%) progressed and 24 patients (14%) died, with 6 months estimated progression-free survival and overall survival being 60.2 and 79%, respectively. Conclusion GBC is an aggressive and lethal malignancy predominantly affecting females in the fifth decade with dismal outcomes. Improved access to health care, an aggressive approach in operable cases, and optimization of systemic and adjuvant therapy are the need of the hour.
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Anuj GuptaObjectives The aim of this study was to do a retrospective analysis of patients of gestational trophoblastic neoplasia (GTN) treated at our center concerning their clinical features and treatment outcomes. Materials and Methods Patients diagnosed and treated from May 2018 to December 2021 were included. All relevant information pertaining to eligible patients was retrieved from the electronic medical records. Patients were risk-stratified based on the World Health Organization (WHO) risk scoring system with a score of seven and above being classified into the high-risk category. Patients were monitored for response by measuring ß-human chorionic gonadotrophin (ß-HCG) levels before each consecutive cycle. Statistical Analysis Appropriate statistical analysis was performed using SPSS version 26. Results Records of 39 eligible patients were analyzed for clinical features out of which 38 were eligible for response assessment. The median age of presentation was 28 years with the majority of patients (79.4%) diagnosed based on ß-HCG levels and clinical history alone. The most common symptom was bleeding per vagina (64%), while the majority of antecedent pregnancies were abortions (59%). Of the 14 low-risk category patients, 12 received single-agent methotrexate/actinomycin D, while 2 received etoposide, methotrexate actinomycin D (EMACO) regimen. Overall response rates were 85.7% with the others responding to the second-line EMACO regimen. Five patients in this group had a WHO score of 5 or 6 and all of them responded to single-agent treatment. Among the 25 high-risk category patients, all received the EMACO regimen with high-dose methotrexate added to those with brain metastasis. The response rate was 87.5% with all the nonresponders having features of ultra-high risk of liver/brain metastasis and/or a WHO score of more than 12. While one nonresponder had expired despite treatment, the other two responded to the etoposide methotrexate and actinomycin D/ etoposide and cisplatin regimen. Conclusion Our results are in consonance with other reported studies. The subcategories of low-risk GTN with a WHO score of 5 and 6 and high-risk GTN with ultra-high-risk features deserve further research in the form of multicenter prospective studies.
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Background: Salivary gland tumours are rare cancers with variable course and prognosis. There is a paucity of data, especially for the advanced stages. Materials and methods: This is a retrospective analysis carried out in our institute. All patients seeking treatment for incurable advanced salivary gland tumours from October 2018 to September 2022 were included. Relevant clinical data were collected and appropriate statistical analysis was applied. Results: 30 patients were included in the analysis. The parotid gland was the most common site of origin (73%). Adenoid cystic carcinoma (ACC) and salivary duct carcinoma (SDC) were equally (37%) the most common pathological subtypes. The majority of patients were males (73%) and lungs (57%) were the most common site of metastases. On molecular analysis, SDC had high rates of androgen receptor (AR) (90%) and human epidermal growth factor receptor 2 (HER2) (55%) positivity. Mucoepidermoid carcinoma (MEC) had AR and HER2 positivity rates of 17% and 20%, respectively, while for ACC it was even lower. A variety of treatment regimens including hormonal therapy, anti-HER2 targeted therapy and chemotherapy were used in first-line treatment. With an overall response rate (ORR) of 10/21 (48%), only 9/21 (43%) went on to receive second-line treatment with an ORR of 4/9 (44%). The progression-free survival (PFS) with first-line treatment (PFS1) was a median of 5 months. The median PFS1 was worst for MEC. The median overall survival (OS) was 10 months. Median OS for ACC, SDC and MEC were 11, 10 and 7 months, respectively. At 24 months, ACC had much higher survival (50%) than others (10%) indicating a proportion of ACC with an indolent course. Conclusion: Our analysis highlights the variable disease biology of advanced salivary gland tumours and throws light on the various possible treatment targets and strategies. Molecular profiling and advancement in targeted therapies are expected to increase survival in this group of rare cancers.
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Background: The data regarding the use of neoadjuvant chemotherapy in technically unresectable head and neck cancer (HNC) is limited and real-world studies are needed to look for the efficacy and toxicities of this approach. Patients and methods: This is a retrospective study conducted in the Medical Oncology department of our hospital. All technically unresectable HNC patients who underwent neoadjuvant chemotherapy between May 2018 and May 2020 were included in this analysis. Patients received three-drug regimen docetaxel, cisplatin and 5-fluorouracil (DCF) regimen, two-drug regimens included docetaxel + cisplatin, paclitaxel + carboplatin both weekly and 3-weekly. The resectability assessment was done clinically and radiologically after completing three neoadjuvant cycles. Overall survival was calculated from the first day of chemotherapy to the date of last follow-up or date of death. Results: A total of 119 patients received neoadjuvant chemotherapy during the specified time. Response assessment showed partial response in 41.9% of patients with three-drug regimens and 37.5% of patients with other regimens. Out of 119 patients, 56 (47%) patients were offered radical intent therapy. Resectability was achieved in 32.3% of three-drug regimen patients and 26.1% of other patients. Surgery was feasible in 33 (27.7%) patients, and postoperative radiotherapy and concurrent chemotherapy were done in 30 patients (25.2%), and surgery with only postoperative radiotherapy was done in 3 patients (2.5%). Radical chemoradiotherapy was done in 23 patients (19.3%). The estimated median survival for patients who could undergo surgery was 18 months [95% confidence interval (CI), 14.9-21.0], and nonsurgical patients were 9 months (95% CI, 7.3-10.6) (p = 0.0001). Conclusion: Our study shows that neoadjuvant chemotherapy in technically unresectable HNC patients can make the disease resectable in around one-third of the patients. The patients who could undergo surgery after neoadjuvant chemotherapy had significantly improved survival as compared to those who could not.
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Objectives Bone marrow aspiration although being a common procedure is associated with significant pain and its reduction remains an unmet need. We evaluated the use of tramadol and eutectic mixture of local anesthetics (prilocaine plus lignocaine) (EMLA) for reducing the severity of pain. Materials and Methods In this pilot study, we compared the addition of either tramadol 50 mg per oral (T) or EMLA local application (E) or no intervention (L) in addition to the usual procedure of local infiltration with lignocaine 2% before bone marrow aspiration and biopsy (BMAB) in adults suspected/confirmed with malignancy. Both, tramadol and EMLA were administered 1 hour prior to the procedure. Primary end point was reduction in pain intensity with these interventions compared with local infiltration alone. Pain was assessed using numerical FACES pain scale, a visual analogue scale. Secondary end points were to see the effect on pre procedure apprehension and to find out the other factors associated with increased pain related to the procedure. Statistical Analysis and Results A total of 300 patients were included in the study, 100 each in tramadol (T), EMLA (E), and only lignocaine local infiltration (L) arms, respectively. The mean pain intensity on the visual scale was significantly lower in the tramadol arm (T, E, L-3.4, 4.4, 4.7, respectively) ( p < 0.0005). There was a significant reduction in percentage of patients who experienced moderate/severe pain (four or more) in the tramadol arm (T, E, L-45, 77, 82%, respectively) ( p < 0.0005). Duration of procedure >10 minutes, body mass index >30, ECOG (Eastern Oncology Group) performance status ≥3, and age >50 years were positively correlated with more pain. Leukemia patients experienced significantly more pain compared with patients with lymphoma and other solid malignancies. Tramadol was well tolerated. No significant effect on pre-procedure apprehension was noted in any of the arms. Conclusion Tramadol appears to have a preventive effect on bone marrow aspiration/biopsy-associated pain and appears to be well tolerated, whereas EMLA was not associated with such an effect. Larger studies may be done to ascertain the same.
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Objective Follicular lymphoma (FL) is a disease of the elderly. It is postulated that younger patients have distinct tumor biology and treatment outcomes. Various lymphoma groups across the world have studied this to understand if young adults (YAs) need a different treatment approach. Our study fills the void in data from an Asian country on YA population with FL. Patients and Methods We retrospectively analyzed young patients (age ≤40 years) diagnosed with FL at our center from 2012 to 2018. Their disease characteristics, treatment details, and outcomes were studied to examine any association between various parameters and survival. Results There were 28 young FL patients included in our study that constituted 14.6% of FL cases (males: 53.5% and females: 46.5%). The median age at diagnosis was 36.5 years. Most of the patients presented in an advanced stage, 57% had extranodal involvement, and 39.3% had bone marrow involvement at the time of presentation. The most common chemotherapy regimen used was cyclophosphamide, vincristine, and prednisone. Half of them received chemoimmunotherapy and only 18% continued rituximab as maintenance therapy. The overall response rate was 92.9% ( n = 26), and the remaining two patients had progressive disease while on treatment. The median progression free survival (PFS) was 6.1 years and median overall survival (OS) was not reached. On univariate analysis, extranodal disease was associated with a lower PFS ( p = 0.06) and low hemoglobin showed a significant association with OS ( p = 0.005). On multivariate analysis, none of the factors showed a significant association with survival. Conclusion Most YAs present with advanced disease with a good response to treatment and favorable outcomes.
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The prognosis of AML is generally poor, with 5-year survival rate of 25%. There has been substantial progress in identification of new therapeutic targets, along with approval of at least three targeted therapies for AML in recent years. Nevertheless, treatment has largely remained unchanged over couple of decades, with ~40% patients not achieving remission. AML is a highly heterogenous disease and there is a need for a preclinical platform to understand the heterogeneity and tumor microenvironment that can guide therapy selection. In this study, we employed an ex vivo tumor explant model to study tumor microenvironment and to select a treatment course for AML patients. Our data reveal dysregulation of DNA methyltransferase (DNMT) and histone deacetylase (HDAC) in a subset of AML patients. Based on this observation, epigenetic modulators azacitidine and panobinostat alone and in combination, were evaluated as treatment regimens in cytarabine refractory tumors. More than 50% of the treated samples showed response to the combination therapy. In order to explore alternate treatment modalities for tumors refractory to these epigenetic modulators, TCGA data analysis was done which revealed increased expression and hypomethylation of IFNGR1/2, suggesting activation of JAK/STAT pathway in AML. This was further interrogated ex vivo, with p-STAT3 expression in patients' samples. Fedratinib, a JAK/STAT inhibitor was evaluated and 78% tumor efficacy response was achieved. Taken together, our data indicate that ex vivo platform derived from patient samples is capable in guiding optimal therapy selection for various classes of drugs including identification of novel targeted therapies.