Landscape of cancer clinical trials in India - a comprehensive analysis of the Clinical Trial Registry-India.

Background: Cancer is one of the leading causes of morbidity and mortality in India. Clinical trials are critical for driving innovation in cancer therapy, diagnosis, and prevention. This study aims to depict the evolving landscape of cancer clinical trials in India by analysing the clinical trials registered in Clinical Trial Registry-India (CTRI). Methods: We identified cancer trials registered in CTRI (between 2007 and 2021) using search terms adapted from the cancer types defined by the National Cancer Institute (USA). We then collated and analysed the publicly available information from CTRI (cancer subtypes, type of trial, treatment intent, type of intervention, sponsor type, recruitment countries) and used descriptive statistics to illustrate the overall as well as year-to-year trend. Findings: In total, we identified 1988 cancer trials, the majority of which focused on treating cancer (63%) and rest of the trials aimed at optimising the operational aspects of surgery (19%), mitigating treatment-related toxicity (10.6%), or treating cancer-related symptoms (7.8%). Focusing on trials with the intent of treating cancer, we found that most were investigating solid tumours as opposed to haematological malignancies with the most prominent cancer subtypes being breast cancer (17%), head and neck cancer (9.8%), lung cancer (9.6%), and cervical cancer (6.6%). The number of trials conducted in a given cancer subtype from our analysis overall correlated to the incidence, mortality, and 5-year prevalence of the respective cancer subtype in India; however, head and neck cancer and cervical cancer were underrepresented in trials as compared with the disease burden. The most common type of intervention was investigational drugs. The most common sponsor types were global pharmaceutical industry (26%) and research institution and hospital (26%). Despite a relatively high cancer burden, the availability of cancer trials in the Northeastern states of India was limited. Interpretation: There is a pressing need for clinical cancer research in India to be better aligned with the nation's healthcare needs and disease burden, focusing on prevalent and deadly cancers while ensuring the availability of clinical trials across geographic regions and underserved populations. Funding: Pi Health USA, a fully owned subsidiary of BeiGene Ltd.

State of cancer care in India and opportunities for innovation.

Cancer is one of the leading causes of morbidity and mortality in India. Despite recent medical and technological advances, the cancer burden in India remains high and continues to rise. Moreover, substantial regional disparities in cancer incidence and access to essential medical resources exist throughout the country. While innovative and effective cancer therapies hold promise for improving patient outcomes, several barriers hinder their development and utilization in India. Here we provide an overview of these barriers, including challenges related to patient awareness, inadequate infrastructure, scarcity of trained oncology professionals, and the high cost of cancer care. Furthermore, we discuss the limited availability of cancer clinical trials in the country, along with an examination of potential avenues to enhance cancer care in India. By confronting these hurdles head-on and implementing innovative, pragmatic solutions, we take an indispensable step toward a future where every cancer patient in the country can access quality care.

Cancer is a major cause of illness and death in India. Despite advances in medicine and technology, the number of people with cancer remains high and continues to increase. There are big differences in access to necessary medical resources across different regions of the country. This article focuses on the barriers that hinder the development and use of effective cancer treatments in India. We discuss challenges related to patient awareness, inadequate medical facilities, a shortage of trained cancer specialists and the high cost of cancer treatment. Additionally, we explore the limited availability of cancer clinical trials in India and potential ways to improve cancer care in the country. By finding innovative and practical solutions to these challenges, we can take a crucial step toward a future where all cancer patients in India have access to high-quality care.

Expert survey on management of prostate cancer in India: Real-world insights into practice patterns.

To gain insights on the diverse practice patterns and treatment pathways for prostate cancer (PC) in India, the Urological Cancer Foundation convened the first Indian survey to discuss all aspects of PC, with the objective of guiding clinicians on optimizing management in PC. A modified Delphi method was used, wherein a multidisciplinary panel of oncologists treating PC across India developed a questionnaire related to screening, diagnosis and management of early, locally advanced and metastatic PC and participated in a web-based survey (WBS) (n = 62). An expert committee meeting (CM) (n = 48, subset from WBS) reviewed the ambiguous questions for better comprehension and reanalyzed the evidence to establish a revote for specific questions. The threshold for strong agreement and agreement was ≥90% and ≥75% agreement, respectively. Sixty-two questions were answered in the WBS; in the CM 31 questions were revoted and 4 questions were added. The panelists selected answers based on their best opinion and closest to their practice strategy, not considering financial constraints and access challenges. Of the 66 questions, strong agreement was reached for 17 questions and agreement was achieved for 22 questions. There were heterogeneous responses for 27 questions indicative of variegated management approaches. This is one of the first Indian survey, documenting the diverse clinical practice patterns in the management of PC in India. It aims to provide guidance in the face of technological advances, resource constraints and sparse high-level evidence.

Biomarkers in Non-Small Cell Lung Cancers: Indian Consensus Guidelines for Molecular Testing.

Novel molecular targets and promising targeted therapies have reshaped diagnostics in patients with advanced non-small cell lung cancer (NSCLC). Despite this progress, the implementation of molecular screening to identify predictive biomarkers in Indian clinical and pathology settings has been challenging due to operational and logistical constraints. This consensus guideline brings together medical oncologists, molecular pathologists and pathologists from India to provide a quick and competent reference for biomarker testing in NSCLC. The guideline summarizes the importance of targetable mutations in NSCLC such as epidermal growth factor receptor (EGFR), rearrangements in anaplastic lymphoma kinase and receptor tyrosine kinase encoded by ROS-1 gene, overexpression of programmed cell death ligand-1 and resistant EGFR mutations. It reaffirms recommendations from international working groups, discusses vulnerable pre-analytical procedures and provides a balanced review on the pros and cons of different diagnostic tests (immunohistochemistry, fluorescence in situ hybridization, polymerase chain reaction-based testing and next-generation sequencing). The document also provides an algorithm to aid diagnostic decision-making and a checklist to assess the quality of testing laboratories that will help the medical oncologists make an informed choice. Overall, these recommendations are based on evidence and clinical experience and will aid policymakers, oncologists, health care practitioners and pathologists who strive to implement molecular strategies and make informed decisions for improved care in NSCLC in India.Funding: AstraZeneca Pharma India Limited.

Survey of Implementation of Antiemetic Prescription Standards in Indian Oncology Practices and Its Adherence to the American Society of Clinical Oncology Antiemetic Clinical Guideline.

PURPOSE: Adherence to international antiemetic prophylaxis guidelines like those of ASCO can result in better control of chemotherapy-induced nausea and vomiting; however, the extent of implementation of such guidelines in India is unknown. Therefore, this survey was planned. METHODS: This study was an anonymized cross-sectional survey approved by the ethics committee. Survey items were generated from the clinical questions given in the ASCO guidelines. The survey was disseminated through personal contacts at an oncology conference and via e-mail to various community oncology centers across India. The B1, B2, and B3 domains included questions regarding the optimal antiemetic prophylaxis for high, moderate, and low-minimal emetogenic regimens. RESULTS: Sixty-six (62.9%) of 105 responded and 65 centers (98.5%) were aware of the published guidelines. The partial, full, and no implementation scores were 92.5%, 4.5%, and 3.0%, respectively. Full implementation was better for the low-minimal emetogenic regimens (34.8%) than the highly emetogenic regimens (6.1%). The three most frequent reasons for hampered implementation of ASCO guidelines in routine chemotherapy practice cited by centers were a lack of sensitization (26 centers; 39.4%), lack of national guidelines (12 centers; 18.2%), and lack of administrative support (10 centers; 15.2%). CONCLUSION: Awareness regarding ASCO antiemetic guidelines is satisfactory in Indian oncology practices; however, there is a need for sensitization of oncologists toward complete implementation of these guidelines in their clinical practice.

Cabazitaxel for Metastatic Castration-Resistant Prostate Cancer: Retrospective Data Analysis from an Indian Centre.

Objective: To determine the efficacy and safety of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) patients from the named patient programme (NPP) at our centre. Methods: mCRPC patients who progressed on docetaxel were given cabazitaxel intravenously every 3 weeks until disease progression or unacceptable toxicity occurred. Overall survival, progression-free survival, prostate-specific antigen response, quality of life (QOL) changes, and safety were reported. Results: Nine men received cabazitaxel (median: 7 cycles; range: 1-27) under the NPP and were followed until death. Median survival was 14.07 months (1.07-23.80) and progression-free survival was 2.67 months (1.07-20.27). QOL was stable for most patients. Common adverse events (grade ≥3) were neutropenia (n = 8), anaemia (n = 4), and leucopenia (n = 4). Conclusion: These data from 9 patients are consistent with the results reported in the TROPIC study with a manageable safety profile.

Preoperative Chemotherapy and Metronomic Scheduling of Chemotherapy in Locally Advanced Oral Cancers.

Locally advanced oral cavity cancers are treated with a multi-modality approach. Surgery is the most efficient local modality in comparison to chemoradiation in oral cancers. Preoperative chemotherapy has failed its expectations to improve disease-free survival or overall survival in resectable oral cancers. Its use as an organ preservation tool is being studied. Induction chemotherapy followed by assessment for surgery is an appropriate option for borderline resectable or technically unresectable oral cancer. Metronomic chemotherapy is being studied as a bridge to surgery and as adjuvant chemotherapy in locally advanced oral cancers. The role of induction chemotherapy in unresectable oral cancers is unproven. Metronomic chemotherapy has shown improved progression-free survival and overall survival in oral cancers in comparison to intravenous cisplatin. A phase 3 study for confirmation of this finding has begun.

Usefulness of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in dermatofibrosarcoma protuberans on treatment with imatinib.

Dermatofibrosarcoma protuberans (DFSP) is a rare locally aggressive tumor with distant metastases being unusual. We present a case of metastatic DFSP treated with imatinib showing complete metabolic response to treatment.

A prospective randomized phase II study comparing metronomic chemotherapy with chemotherapy (single agent cisplatin), in patients with metastatic, relapsed or inoperable squamous cell carcinoma of head and neck.

BACKGROUND: Cetuximab based treatment is the recommended chemotherapy for head and neck squamous cell cancers in the palliative setting. However, due to financial constraints, intravenous (IV) chemotherapy without cetuximab is commonly used in lesser developed countries. We believe that oral metronomic chemotherapy may be safer and more effective in this setting. METHODS: We conducted an open label, superiority, parallel design, randomized phase II trial comparing oral MCT [daily celecoxib (200mg twice daily) and weekly methotrexate (15mg/m(2))] to intravenous single agent cisplatin (IP) (75mg/m(2)) given 3 weekly. Eligible patients had head and neck cancers requiring palliative chemotherapy with ECOG PS 0-2 and adequate organ functions who could not afford cetuximab. The primary end point was progression-free survival. RESULTS: 110 Patients were recruited between July 2011 to May 2013, 57 randomized to the MCT arm and 53 to the IP arm. Patients in the MCT arm had significantly longer PFS (median 101 days, 95% CI: 58.2-143.7 days) compared to the IP arm (median 66 days, 95% CI; 55.8-76.1 days) (p=0.014). The overall survival (OS) was also increased significantly in the MCT arm (median 249 days, 95% CI: 222.5-275.5 days) compared to the IP arm (median 152 days, 95% CI: 104.2-199.8 days) (p=0.02). There were fewer grade 3/4 adverse effects with MCT, which was not significant. (18.9% vs. 31.4%, P=0.14). CONCLUSION: Oral metronomic chemotherapy has significantly better PFS and OS than single agent platinum in the palliative setting.

Compliance With Neoadjuvant Chemotherapy in T4 Oral Cancers: Place, Person, Socioeconomic Status, or Assistance.

PURPOSE: Approximately 15% to 20% of our patients with head and neck cancer receiving neoadjuvant chemotherapy (NACT) discontinue therapy because of various nonmedical reasons. We sought to analyze the factors associated with treatment default and noncompliance among these patients. PATIENTS AND METHODS: We performed a retrospective analysis of patients with T4 oral cancer treated with NACT between January 2011 and December 2012. We included patients who discontinued treatment for nonmedical reasons before the second cycle of NACT. The factors analyzed were income, education, socioeconomic status, age, sex, place of residence, habits, and payment pattern (government supported or personal capacity). Pearson χ2 test was used to identify significant factors associated with noncompliance. RESULTS: Of 486 patients, 91 patients (18.7%) were noncompliant. Percentages of noncompliant patients in the age groups < 30, between 30 and 60, and > 60 years were 25.0%, 17.4%, and 25.5%, respectively (P = .27). Percentages of noncompliance in patients residing within the city, same state, or different state were 20.7%, 20.9%, and 17.1%, respectively (P = .44). Noncompliance rates were 20.3%, 15.7%, 18.1%, and 22.5% in upper middle, lower middle, upper lower, and lower economic strata, respectively (P = .60). Similarly, there was no significant difference in noncompliance according to occupation, education level, payment pattern, sex, or habits. CONCLUSION: Our analysis failed to identify any specific significant factor associated with noncompliance with NACT among our patients with T4 oral cancers.

Induction chemotherapy in technically unresectable locally advanced carcinoma of maxillary sinus.

Background. Locally advanced carcinoma of maxillary sinus has been historically reported to have poor prognosis. We evaluated the role of NACT in improving the outcome in these patients. Methods. 41 patients with locally advanced technically unresectable (stage IVa) or unresectable maxillary carcinoma (stage IVb) were treated with induction chemotherapy between 2008 and 2011. The demographic profile, response and toxicity of chemotherapy, definitive treatment received, progression free survival (PFS), and overall survival (OS) were analyzed. Univariate and multivariate analysis were performed to determine factors associated with PFS and OS. Results. The chemotherapy included two drugs (platinum and taxane) in 34 patients (82.9%) and three drugs (platinum, taxane, and 5 FU) in 7 (17.1%). There was no complete response seen in any of the patients, stable disease in 18 (43.9%), partial response in 16 (39%), and progression in 7 (17.1%) patients. After induction, the treatment planned included surgery in 12 (29.3%), CT-RT in 24 (58.5%), radical RT in 1 (2.4%), palliative RT in 1 (2.4%), and palliative chemotherapy in 3 (7.3%) patients. Overall, the median PFS was 10.0 months. The OS at 24 months and 36 months was 41% and 35%, respectively. Conclusion. In unresectable maxillary carcinoma, induction chemotherapy has clinically significant benefit with acceptable toxicity.

Weekly chemotherapy as Induction chemotherapy in locally advanced head and neck cancer for patients ineligible for 3 weekly maximum tolerable dose chemotherapy.

OBJECTIVE: To study the safety and efficacy of weekly chemotherapy as part of induction chemotherapy, in locally advanced head and neck cancer for patients, who are unfit for upfront radical treatment. MATERIALS AND METHODS: It is a retrospective analysis of on-use weekly chemotherapy as Induction chemotherapy in locally advanced head and neck cancer, who are technically unresectable are unfit for upfront radical treatment. Induction chemotherapy given was a 2 drug combination of paclitaxel (80 mg/m 2 ) and carboplatin AUC 2. The decision to give weekly induction chemotherapy was given on the basis of presence of 2 more following features: Poor performance status (ECOG PS 2-3), presence of uncontrolled co morbidities, BMI below 18.5 kg/m 2 and age more than 60 years. The Statistical Package for the Social Sciences software (SPSS version 16.0) was used for analysis. The response rates, toxicity (accordance with CTCAE vs. 4.02), completion rate (Cp) of radical intent treatment post neoadjuvant chemotherapy (NACT), progression-free survival (PFS) and overall survival (OS) are reported. RESULTS: Fifteen patients were considered for such therapy. Fourteen out of fifteen patients completed NACT. The median numbers of planned weekly cycles were 6 (3-8). Response (CR + PR) was seen in 10 patients. Overall grade 3-4 toxicity was seen in 6 patients. No toxicity related mortality was noted. The calculated completion rate (Cp) of radical intent treatment post NACT was 46.7%. The median PFS and OS were 10.36 months (95% CI 6.73-14.00 months) and 16.53 months (95% CI 4.22-28.84). CONCLUSION: Use of induction chemotherapy with weekly regimen is safe and effective selected cohort of patients with locally advanced disease who are unfit for upfront radical treatment.

Palliative chemotherapy in carcinoma penis: Does platinum and taxane combination holds a promise?

AIM: To report safety and efficacy of chemotherapy incorporating the combination of paclitaxel and platinum in patients with advanced penile carcinoma. MATERIALS AND METHODS: Retrospective analysis of patient with advanced penile carcinoma undergoing palliative chemotherapy with paclitaxel and platinum combination. The demographic profile, indication of treatment, chemotherapy details, toxicity and survival outcome were noted. Statistical analysis was done for estimation of progression free survival and overall survival. Factors affecting these outcomes were sought for. RESULTS: Eighteen patients with a median age of 47.5 years (31-68 years) were offered palliative intent chemotherapy over a period of 2.5 years. ECOG performance was 1 in 12 patients (66.7%) and 2 in 6 patients (33.3%). The grade of tumor was poorly differentiated in 8 patients (44.4%), moderately differentiated in 5 (27.8%) and we1l differentiated in 5 patients (27.8%). Twelve patients had previous surgical treatment (66.7%), with 2 of them having received groin radiation in past. The indication for treatment was metastatic disease in 7 patients (38.9%) and locally advanced disease in 11 patients (61.1%). Out of 18 patients 13 received chemotherapy. Paclitaxel and carboplatin combination was given in 10 patients (76.9%) while paclitaxel and cisplatin was received by 3 patients (23.1%). The median numbers of cycles received were 3 (1-6 cycles). Response rate was 30.8%. The median estimated progression free survival (PFS) and overall survival (OS) for patients receiving atleast one cycle of chemotherapy (n = 13) were 96 days and 246 days respectively. Among tested variables the median OS in patients who had received 2 or more cycles was 351 days versus 55 days in those who received less than 2 cycles (P = 0.025). However, after applying Bonferroni correction, the difference was no longer significant. There was no toxicity related death or life threatening complication. CONCLUSION: Our institutional protocol of platinum-based doublet with paclitaxel is effective, well-tolerated and has the advantage being delivered on an outpatient basis alone. Overall, we believe that paclitaxel-platinum is an effective regimen that needs to be investigated further in larger studies.

Management of isolated recurrence of extramedullary myeloid tumor at a single site.

Extramedullary myeloid tumors (EMMT) can precede, occur with or follow AML. Rarely, they can present as isolated relapses. We present a 9-year-old child with t (8, 21) positive AML who was treated with induction regimen and achieved remission. While on high-dose cytarabine consolidation, he had isolated relapse in a single cervical lymph node with uninvolved marrow. He was treated with salvage chemotherapy alone. There are no clear guidelines for treatment of isolated extramedullary relapse. Chemotherapy, radiotherapy followed by stem cell transplant is the usual option. Our patient is unique for the unusual site of relapse and prolonged remission with cladribine-based chemotherapy, mitoxantrone-based consolidation, and oral maintenance therapy.

Induction chemotherapy in locally advanced pharyngolaryngeal cancers with stridor: is it feasible and safe?

Background. The standard initial management of patients with locally advanced pharyngolaryngeal presenting with stridor is tracheostomy. Tracheostomy has been shown to negatively impact cancer-related outcomes. Methods. Retrospective analysis of prospectively collected data of 9 patients, who underwent induction chemotherapy with the aim of prevention of tracheostomy. Presenting features, time to resolution of stridor, and further management are reported. Results. Eight out of 9 patient received chemotherapy within 12 hours of presentation with stridor. There were 4 patients each with primary hypopharynx and larynx. The stage was IVA in 6 patients and IVB in 2 patients. In all patients receiving immediate chemotherapy, clinical stridor resolved within 48 hours. The radiological response rate was 62.5%. The median reduction in size of tumor was 37%. Conclusion. Immediate neoadjuvant chemotherapy is a feasible and safe option for patients presenting with early stridor and helps in resolution of stridor and avoiding tracheostomy.