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Olanzapine is an effective antiemetic agent but it results in substantial daytime somnolence when administered at the standard dose. Our aim was to compare the efficacy of low-dose versus standard-dose olanzapine after highly emetogenic chemotherapy in patients with solid tumours. This was a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial done in a tertiary care referral centre in India (Tata Memorial Centre, Homi Bhabha National Institute, Mumbai). Patients aged 13–75 years with an Eastern Cooperative Oncology Group performance status of 0–2, who were receiving doxorubicin–cyclophosphamide or high-dose cisplatin for a solid tumour were eligible. Patients were randomly assigned (1:1), with block randomisation (block sizes of 2 or 4) and stratified by sex, age (≥55 or <55 years), and chemotherapy regimen, to receive low-dose (2·5 mg) oral olanzapine or standard-dose (10·0 mg) oral olanzapine daily for 4 days, in combination with a triple antiemetic regimen. Study staff were masked to treatment allocation but patients were aware of their group assignment. The primary endpoint was complete control, defined as no emetic episodes, no rescue medications, and no or mild nausea in the overall phase (0–120 hours), assessed in the modified intention-to-treat (mITT) population (ie, all eligible patients who received protocol-specified treatment, excluding those who had eligibility violations and who withdrew consent after randomisation). Daytime somnolence was the safety endpoint of interest. Non-inferiority was shown if the upper limit of the one-sided 95% CI for the difference in the complete control proportions between the treatment groups excluded the non-inferiority margin of 10%. This study is registered with the Clinical Trial Registry India, CTRI/2021/01/030233, is closed to accrual, and this is the final data analysis. Between Feb 9, 2021, and May 30, 2023, 356 patients were pre-screened for eligibility, of whom 275 patients were enrolled and randomly assigned (134 to the 2·5 mg olanzapine group and 141 to the 10·0 mg olanzapine group). 267 patients (132 in the 2·5 mg group and 135 in the 10·0 mg group) were included in the mITT population, of whom 252 (94%) were female, 15 (6%) were male, and 242 (91%) had breast cancer. 59 (45%) of 132 patients in the 2·5 mg olanzapine group had complete control in the overall phase versus 59 (44%) of 135 in the 10·0 mg olanzapine group (difference –1·0% [one-sided 95% CI –100·0 to 9·0]; p=0·87). In the overall phase, there were significantly fewer patients in the 2·5 mg olanzapine group than in the 10·0 mg olanzapine group with daytime somnolence of any grade (86 [65%] of 132 vs 121 [90%] of 135; p<0·0001) and of severe grade on day 1 (six]5%] vs 54 [40%]; p<0·0001). Our findings suggest that olanzapine 2·5 mg is non-inferior to 10·0 mg in antiemetic efficacy and results in reduced occurrence of daytime somnolence among patients receiving highly emetic chemotherapy and should be considered as a new standard of care. Progressive Ladies Welfare Association.

There is scant data from India on efficacy and safety of palbociclib and ribociclib in routine clinical practice. This retrospective, observational, single institution study included patients with estrogen and/or progesterone receptor positive and human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancers, who received palbociclib or ribociclib with any partner endocrine therapy in any line of treatment between January 2016 and June 2019. Data were analyzed for progression-free survival (PFS), overall survival (OS) and toxicity. The study included 101 female patients with median age of 57 (IQR 48-62) years, of whom 80 (79.2%) were postmenopausal, 79 (78.2%) received palbociclib or ribociclib in second- or later-line treatment, 59 (58.4%) received fulvestrant and 41 (40.6%) received an aromatase inhibitor. In first-line treatment, at a median follow-up of 21.7 (0.5-41.9) months, median PFS and OS were 21.1 (95%CI 16.36-not estimable) months and not reached, respectively. In second- or later-line setting, at a median follow-up of 17.2 (0.5-43.7) months, median PFS and OS were 5.98 (95%CI 4.96-7.89) months and 20.2 (95%CI 14.1-not estimable) months, respectively. Grade 3-4 neutropenia and febrile neutropenia were seen in 45 (45.0%) and 9 (9.0%) patients, respectively while dose reduction was required in 32 (31.7%) patients. In multivariable Cox regression analysis, first-line setting (HR 0.49, 95%CI 0.25-0.97, p = 0.043) and ECOG performance status 1 (HR 0.43, 95%CI 0.20-0.91, p = 0.028) were significantly associated with PFS while only ECOG PS 1 was significantly associated (HR 0.04, 95%CI 0.008-0.206, p = 0.000) with OS. Palbociclib and ribociclib, when used in routine clinical practice in first or subsequent lines of treatment, resulted in efficacy and toxicity outcomes in concordance with those expected from pivotal trials.

There is sparse data on the outcomes of combined chemotherapy and hormonal therapy (CHT) in patients with metastatic breast cancer (MBC). This retrospective analysis of HR-positive, HER2-negative MBC patients treated between January 2015 and December 2020 with a combination of chemotherapy (capecitabine or oral cyclophosphamide) and hormonal therapy evaluated their progression-free survival (PFS) and overall survival (OS).The study included 224 patients with a median age of 53 (26–91) years, a median of 3 (0–12) prior treatment lines and a median follow-up of 21.2 (1.7–87.0) months. There were 195 (87.1%) PFS events and 154 (68.8%) deaths, with a median PFS of 8.8 (95% CI 7.0-10.6) months and a median OS of 16.7 (95% CI 13.5–19.9) months. In univariable analyses, ECOG PS (≤ 1 vs. ≥ 2, PFS 14.9 vs. 6.0 months, HR 0.32, 95% CI 0.23–0.44, p  < 0.001; OS 36.2 vs. 11.0 months, HR 0.29, 95% CI 0.20–0.42, p  < 0.001) and duration of most recent endocrine therapy (> 12 vs. ≤ 12 months, PFS 11.7 vs. 6.9 months, HR 0.32, 95% CI 0.23–0.44, p  = 0.023; OS 21.9 vs. 15.0 months, HR 0.70, 95% CI 0.49–0.99, p  = 0.047) were significantly associated with survival. In multivariable Cox analyses, better ECOG PS (HR 0.29, 95% CI 0.19-0.43, p<0.001) and capecitabine-based chemotherapy (HR 0.60, 95% CI 0.37-0.99, p=0.043) were significantly associated with higher OS. The chemo-hormonal therapy regimens were well tolerated, with 21 (9.4%) patients experiencing any grade ≥3 toxicity. Chemo-hormonal therapy is an effective treatment in heavily pre-treated MBC patients, including those with visceral metastases. Trial registration: CTRI/2022/01/039242

ImportanceThe Cancer Aging Research Group (CARG) toxicity score is used to assess toxicity risk in geriatric patients receiving chemotherapy.ObjectiveThe primary aim was to validate the CARG score in geriatric patients treated with curative intent chemotherapy in predicting grade 3–5 toxicities.DesignThis was a longitudinal prospective observational study.SettingTata Memorial Hospital, Mumbai, India, a tertiary cancer care referral centre.ParticipantsPatients, aged ≥65 years, with gastrointestinal, breast or gynaecological stage I–III cancers being planned for curative intent chemotherapy. A total of 270 patients were required for accrual in the study.Exposure(s)Total risk score ranged from 0 (lowest toxicity risk) to 19 (highest toxicity risk).Main outcome(s) and measure(s)The primary endpoint of the study was to evaluate whether the CARG risk score predicted for grade 3–5 toxicities.ResultsThe study cohort of 270 patients had a mean age of 69 (65–83) years, with the most common cancers being gastrointestinal (79%). Fifty-two per cent of patients had atleast one grade 3–5 toxicity. The risk of toxicity was increased with an increasing risk score (42% low risk, 51% medium risk and 79% high risk; p<0.001). There was no association between either Eastern Cooperative Oncology Group (ECOG) performance status (p=0.69) or age-adjusted Charlson Comorbidity Index (p=0.79) risk categories and grade 3–5 chemotherapy toxicities.Conclusions and relevanceThis study validates the CARG risk score in predicting for grade 3–5 toxicities in geriatric oncology patients receiving curative intent chemotherapy and can be considered as the standard of care before planning chemotherapy in every elderly patient.Trial registration numberCTRI/2016/10/007357; Results.

IntroductionIn locally advanced cervical cancer, nodal, local and distant relapse continue to be significant patterns of relapse. Therefore, strategies to improve the efficacy of chemoradiation are desirable such as biological pathway modifiers and immunomodulating agents. This trial will investigate the impact of nelfinavir, a protease inhibitor that targets the protein kinase B (AKT) pathway on disease-free survival (DFS).Methods and analysisRadiosensitising effect of nelfinavir in locally advanced carcinoma of cervix is a single-centre, open-label, parallel-group, 1:1 randomised phase-III study. Patients aged over 18 years with a diagnosis of carcinoma cervix stage III are eligible for the study. After consenting, patients will undergo randomisation to chemoradiation and brachytherapy arm or nelfinavir with chemoradiation and brachytherapy arm. The primary aim of the study is to compare the difference in 3-year DFS between the two arms. Secondary aims are locoregional control, overall survival, toxicity and quality of life between the two arms. Pharmacokinetics of nelfinavir and its impact on tumour AKT, programmed cell death ligand 1, cluster of differentiation 4, cluster of differentiation 8 and natural killer 1.1 expression will be investigated. The overall sample size of 348 with 1 planned interim analysis achieves 80% power at a 0.05 significance level to detect a HR of 0.66 when the proportion surviving in the control arm is 0.65. The planned study duration is 8 years.Ethics and disseminationThe trial is approved by the Institutional Ethics Committee-I of Tata Memorial Hospital, Mumbai (reference number: IEC/0317/1543/001) and will be monitored by the data safety monitoring committee. The study results will be disseminated via peer-reviewed scientific journals, and conference presentations. Study participants will be accrued after obtaining written informed consent from them. The confidentiality and privacy of study participants will be maintained.Trial registration numberThe trial is registered with Clinical Trials Registry-India (CTRI/2017/08/009265) and ClinicalTrials.gov (NCT03256916).

Denovo metastatic young breast cancer (dnmYBC), defined as age <40 years, is a challenging entity, with a significant burden and sparse data from low and middle-income countries. We analysed the prospectively collected data of dnmYBC women from 2015 to 2016. There were 188 dnmYBC with a median age of 35.5 years. Of these, hormone receptor positive (HR+) were 72 (38.3) %, triple-negatives (TNBC) were 45 (23.9) %, Human Epidermal Growth Factor Positive (HER2+) were 42 (22.4) % and triple positives were 29 (15.4) %. TNBC women predominantly had visceral 40 (88.9%) metastasis, HR+ had nodal 51 (70.8%) and skeletal 10 (13.8%), while HER2+ women had higher brain metastasis (BM) 16 (38.1%).At a median follow-up of 39.8 [Interquartile range (IQR): 24-55.5] months, the median event-free survival (EFS) was 9.3 (95% CI; 8.1-10.4) months for the entire cohort and 1-year, 2-year and 3-year predicted EFS were 47.8%, 13.4% and 3%, respectively. The median EFS was superior in HR+ women.[15.7 months, hormone receptor (HR)-0.53;95% CI-9.8-21.7; p-0.013] versus (11.4 months, 95 %CI-5.9-16.8) in TNBC versus (7.7 months, 95% CI-6.0-9.5) in HER-2 + women and without BM at baseline [9.3 versus 3.0 months (with BM), HR-5.65; CI-1.72-17.9; -0.001]. Median EFS was superior in the treatment-naïve (155, 82.4%) versus prior-treated (33, 17.5%) women, 35.5 (95% CI:12.24-58.72) versus 12.4 (95% CI:11.45-13.51) months; -0.000]. The HER2+ women who received targeted therapy in the first line had a significantly superior median EFS of 13.0 versus 7.7 months (HR -0.465:CI 0.22-0.57: -0.038). Denovo mYBC is associated with an aggressive course, poor prognosticators include HR negative disease, brain metastasis, inadvertent prior treatment and inadequate access to targeted therapies. Early diagnosis, prompt treatment and expanding accessibility are warranted to improve care.

Abstract The incidence of breast cancer is increasing rapidly in urban India due to the changing lifestyle and exposure to risk factors. Diagnosis at an advanced stage and in younger women are the most concerning issues of breast cancer in India. Lack of awareness and social taboos related to cancer diagnosis make women feel hesitant to seek timely medical advice. As almost half of women develop breast cancer at an age younger than 50 years, breast cancer diagnosis poses a huge financial burden on the household and impacts the entire family. Moreover, inaccessibility, unaffordability, and high out-of-pocket expenditure make this situation grimmer. Women find it difficult to get quality cancer care closer to their homes and end up traveling long distances for seeking treatment. Significant differences in the cancer epidemiology compared to the west make the adoption of western breast cancer management guidelines challenging for Indian women. In this article, we intend to provide a comprehensive review of the management of breast cancer from diagnosis to treatment for both early and advanced stages from the perspective of low-middle-income countries. Starting with a brief introduction to epidemiology and guidelines for diagnostic modalities (imaging and pathology), treatment has been discussed for early breast cancer (EBC), locally advanced, and MBC. In-depth information on loco-regional and systemic therapy has been provided focusing on standard treatment protocols as well as scenarios where treatment can be de-escalated or escalated.

To synthesize the role of secondary cytoreduction in recurrent ovarian cancer from the results of randomized studies. We conducted a meta-analysis of randomized controlled trials which compared secondary cytoreductive surgery versus no surgery in patients with platinum sensitive relapsed ovarian cancer. Individual patient data for overall survival and progression free survival were manually extracted from published survival curves, for whole study populations and subgroups based on completeness of surgical resection and bevacizumab use, using WebPlotDigitizer software. Overall survival and progression free survival curves for each study and the combined population were reconstructed from extracted data. Three studies with 1249 patients were included, of whom complete resection was achieved in 427 (34.2%) patients. In individual patient data analysis of the whole study population with 562 deaths, there was no significant difference in overall survival between the surgery and no surgery groups (median 52.8 vs 52.1 months, respectively, hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.80 to 1.11; p=0.5) but the surgery group had significantly longer progression free survival compared with the no surgery group (median 18.3 vs 14.4 months, respectively, HR 0.70, 95% CI 0.62 to 0.80; p<0.001). In subgroup analyses, overall survival was significantly longer in the complete cytoreduction subgroup compared with the no surgery group (median 62.0 vs 52.1 months, respectively, HR 0.70, 95% CI 0.57 to 0.92; p<0.001) while overall survival was significantly worse in the incomplete cytoreduction subgroup compared with the no surgery group (median 34.2 vs 52.1 months, respectively, HR 1.72, 95% CI 1.38 to 2.14; p<0.001). In the no bevacizumab subgroup, there was no significant overall survival difference between the surgery and no surgery groups (median 49.3 vs 47.0 months, HR 0.86, 95% CI 0.67 to 1.10; p=0.25). Secondary cytoreductive surgery among women with platinum-sensitive relapsed ovarian cancer did not lead to significant benefit in overall survival although it increased progression free survival. However, overall survival was significantly longer among patients in whom complete cytoreduction was possible compared with no surgery.

OBJECTIVETo investigate differences in standard clinico-radiological evaluation versus Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for reporting survival outcomes in patients with locally advanced cervical cancer treated with chemoradiation and brachytherapy.METHODSBetween November 2017 and March 2020, patients recruited in cervical cancer trials were identified. MRI at diagnosis and at least one follow-up imaging was mandatory. Disease-free survival and progression-free survival were determined using standard evaluation (clinical examination and symptom-directed imaging) and RECIST 1.1. Agreement between criteria was estimated using κ value. Sensitivity analysis was done to test the sensitivity, specificity, and accuracy of RECIST 1.1 in detecting response to treatment.RESULTSSixty-nine eligible patients had at least one target lesion. Thirty-three patients (47.8%) had pathological lymph nodes. Of these 33 patients, RECIST 1.1 classified only 18% (6/33) as ‘target nodal lesions’ and the remaining nodes as ‘non-target’. There were 6 (8.7%) and 8 (11.6%) patients with disease events using RECIST 1.1 and standard evaluation, respectively. The disease-free survival at 12, 18, and 24 months using RECIST 1.1 was 94.2%, 91.2%, 91.2%, and with standard evaluation was 94.2%, 89.7%, and 88.2%, respectively (p=0.58). Whereas, progression-free survival at 12, 18, and 24 months using RECIST 1.1 and standard evaluation were same (94.2%, 91.2%, and 91.2%, respectively). The κ value was 0.84, showing strong agreement in assessing disease-free survival, although an absolute difference of 3% between endpoint assessment methodologies. RECIST 1.1 had a sensitivity of 75% (95% CI 34.91% to 96.81%), specificity of 100% (95% CI 94.13% to 100%), and accuracy of 97.1% (95% CI 89.92% to 99.65%).CONCLUSIONSThe study showed 1.5% and 3% difference in disease-free survival at 18 and 24 months and no difference in progression-free survival between RECIST 1.1 and standard evaluation in a patient cohort with low event rate.