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1.
Indian J Cancer ; 59(Supplement): S142-S159, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35343198

RESUMO

Androgen deprivation therapy (ADT) using gonadotropin-releasing hormone agonist (s) (GnRH-A) remains the backbone of advanced prostate cancer treatment. In this review, we assessed the efficacy, safety, and convenience of administration of various GnRH-A. All GnRH-A (goserelin, triptorelin, buserelin, histrelin, and leuprorelin) have comparable potential to suppress testosterone (T) levels (≤50 ng/dL in a month and ≤20 ng/dL in 3 months). However, goserelin has shown better efficacy in maintaining T levels ≤50 ng/dL compared with leuprolide. The incidences of T escape are lower with goserelin and leuprolide than buserelin. Goserelin also has maximum benefit in prostate-specific antigen suppression. In neoadjuvant setting, when only goserelin was used, the 10-year overall survival (OS) rate was 42.6% to 86%. When either goserelin or leuprolide was used, the 10-year OS rate was 62%. As an adjuvant to radical prostatectomy, goserelin had a 10-year survival rate of 87%, and triptorelin had an 8-year survival rate of 84.6%. Goserelin further showed an absolute survival rate of 49% when used as an adjuvant to radiotherapy. The survival rates further improved when GnRH-A are used as combined androgen blockade compared with monotherapy. The frequency and severity of adverse events (hot flushes, fatigue, sexual dysfunction) are comparable among the GnRH-A. Goserelin appears to be the most convenient of all the GnRH-A for administration. Lack of conclusive comparative evidence makes it imperative to have a holistic approach of considering the patient profile and the disease characteristics to select the appropriate GnRH-A for ADT in prostate cancer.


Assuntos
Antagonistas de Androgênios , Neoplasias da Próstata , Hormônio Liberador de Gonadotropina , Gosserrelina/efeitos adversos , Gosserrelina/uso terapêutico , Humanos , Leuprolida/efeitos adversos , Leuprolida/uso terapêutico , Masculino , Neoplasias da Próstata/tratamento farmacológico
2.
Ecancermedicalscience ; 15: 1274, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567259

RESUMO

BACKGROUND: A significant proportion of non-small cell lung cancer (NSCLC) patients present with poor performance status (PS) at baseline are almost always excluded from the clinical trials leading to availability of only limited data in this subgroup. PATIENTS AND METHODS: This was an observational single institutional study. The eligibility criteria for inclusion were a histologic or cytologic diagnosis of advanced NSCLC and Eastern Cooperative Oncology Group PS 3 or 4. All patients coming between June 2015 and December 2018 were evaluated for inclusion in this study. RESULTS: A total of 245 patients were enrolled in the study. The median age of the patients was 63 years (range 25-89), 142 (58%) were male, 196 (80%) had adenocarcinoma histology and 192 (78.4%) has PS 3 while rest (21.6%) had PS 4. Out of 245 patients, 192 (78.4%) received oral tyrosine kinase inhibitors (TKI) and supportive care, 45 (18.4%) received supportive care alone, while 8 (3.2%) patients received chemotherapy along with supportive care. Median overall survival (OS) was 3 months (95% CI: 1.8-4.2) in patients who received oral TKI versus 1 month (1.0-2.9) in patients who received supportive care alone (log-rank p = 0.013). The median OS for epidermal growth factor receptor (EGFR) mutant patients who received oral TKI was 12 months (95% CI: 7.7-16.3), while it was 3 months (95% CI: 1.5-4.5) for patients who were EGFR wild-type and received TKI on compassionate basis (HR = 0.50; 95% CI: 0.32-0.77; p = 0.001). CONCLUSIONS: The use of oral TKI on a compassionate basis led to improvement in survival in the overall cohort of the patients; this was principally driven by EGFR-mutated patients.

3.
Cancer Med ; 10(5): 1525-1534, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33591635

RESUMO

BACKGROUND: Checkpoint inhibitors (Nivolumab and Pembrolizumab) are approved for multiple indications in solid tumors. However access to these therapies is limited in low and middle income countries. Hence we performed an audit to identify accessibility, adverse event rates, compliance, progression free survival and overall survival in solid tumors. METHODS: This was a single center retrospective analysis of prospective data base of patients with non-melanoma solid tumors who were treated with immunotherapy from August 2015 to November 2018. Adverse events during immunotherapy were documented and graded using CTCAE (Common terminology criteria for adverse events), v. 4.02. The response rates to immunotherapy, toxicities and the time to onset and resolution of toxicities were also evaluated as secondary endpoints. RESULTS: Out of 9610 patients, only 155 patients (1.61%) could receive immunotherapy. The most common malignancies included metastatic non-small cell lung cancer, metastatic renal cell carcinoma, metastatic urothelial carcinoma and relapsed/recurrent head and neck squamous cell carcinoma. Median overall survival in patients who received immunotherapy in non-melanoma solid malignancies was 5.37 months (95% CI, 3.73-9.73). Poor performance status at baseline was the only adverse prognostic factor. The median progression free survival was 2.57 months (95% CI, 1.73-3.83). Immunotherapy was well tolerated with most common side effects being fatigue 14.8% and anorexia 5.8%. The cumulative incidence of immune related adverse events like hepatitis, pneumonitis, colitis and nephritis was less than 10%. CONCLUSION: Real-world data in Indian setting confirms the benefit of immunotherapy in patients with advanced non-melanoma solid tumors.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia Adotiva/estatística & dados numéricos , Neoplasias/tratamento farmacológico , Nivolumabe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anorexia/induzido quimicamente , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Fadiga/induzido quimicamente , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/provisão & distribuição , Índia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/patologia , Nivolumabe/efeitos adversos , Intervalo Livre de Progressão , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Adulto Jovem
4.
Ecancermedicalscience ; 15: 1318, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35047069

RESUMO

BACKGROUND: Oral mucositis related pain during CTRT in head and neck cancers is a common problem. Unfortunately, in spite of it being common, there is limited evidence for selection of systemic analgesic in this situation. Hence, this study was designed to compare the analgesic effect of a non-steroidal anti-inflammatory drug (diclofenac) versus a weak opioid (tramadol). PATIENTS AND METHODS: This was an open-label, parallel design, superiority randomised controlled study. In this study, head and neck cancer patients undergoing radical or adjuvant chemoradiation, who had grade 1 or above mucositis (in accordance with Common Terminology Criteria for Adverse Events version 4.03) and had pain related to it were randomly assigned to either diclofenac or tramadol for mucositis related pain control. The primary endpoint was analgesia after the first dose. The secondary endpoints were the rate of change in analgesic within 1 week, adverse events and quality of life. RESULTS: One hundred and twenty-eight patients were randomised, 66 in diclofenac and 62 in tramadol arm. The median area under the curve for graph of pain across time after first dose of pain medication for the diclofenac arm and the tramadol arm was 348.936 units (range: 113.64-1,969.23) and 420.87 (101.97-1,465.96), respectively, (p = 0.05619). Five patients (8.1%) in the tramadol arm and 11 patients (16.7%) in the diclofenac arm required a change in analgesic within 1 week of starting the analgesic (p = 0.184). There was no statistically significant difference in any adverse events between the two arms. However, the rate of any grade of renal dysfunction was numerically higher in the diclofenac arm (10.6% versus 4.8%, p = 0.326). CONCLUSION: In this phase 3 study, evaluating diclofenac and tramadol for chemoradiation induced mucositis pain, there was no statistical difference in analgesic activity of these two drugs.

5.
Med Oncol ; 37(5): 48, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32277283

RESUMO

Therapy-related acute leukemias (t-ALs) represent approximately 10-20% of all acute leukemias, are frequently resistant to chemotherapy, and are associated with guarded outcomes. The national comprehensive cancer network data suggest that t-AL cases are diagnosed at increasing rates in breast cancer patients treated with chemotherapeutic agents targeting topoisomerase II. Two cases of BRCA1-mutated ovarian and breast carcinoma who developed therapy-related APL and ALL, respectively, following topoisomerase II-directed therapy were characterized. Genomic characterization of therapy-related acute promyelocytic leukemia (t-APL) revealed a unique RARA intron 2 breakpoint (Chr17: 40347487) at 3'-end of RARA corroborating breakpoint clustering in t-APL following topoisomerase II inhibition. Both cases of this series harbored germline BRCA1 mutations. The germline BRCA1 mutation in patient with t-APL was detected in exon 8 (HGVS nucleotide: c.512dupT). This mutation in t-APL is extremely rare. Interestingly, t-ALL patient in this series had a BRCA1 mutation (HGVS nucleotide: c.68_69delAG; BIC designation: 187delAG) identical to a previously reported case after the treatment of same primary disease. It is unlikely that two breast cancer patients with identical BRCA1 mutation receiving topoisomerase II-targeted agents for the primary disease developed t-AL by chance. This report highlights the development of t-AL in BRAC1-mutated hereditary breast and ovarian cancer patients and warrants further studies on functional consequences of topoisomerase inhibition in this setting.


Assuntos
Proteína BRCA1/genética , Carcinoma/tratamento farmacológico , Síndrome Hereditária de Câncer de Mama e Ovário/tratamento farmacológico , Leucemia Mieloide Aguda/induzido quimicamente , Inibidores da Topoisomerase II/efeitos adversos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/genética , Carcinoma/patologia , Feminino , Mutação em Linhagem Germinativa , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Síndrome Hereditária de Câncer de Mama e Ovário/patologia , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Inibidores da Topoisomerase II/uso terapêutico , Translocação Genética , Resultado do Tratamento
6.
Eur J Surg Oncol ; 46(6): 1052-1058, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32014275

RESUMO

BACKGROUND: Studies reporting outcomes of salvage surgery in locally advanced head and neck squamous cell carcinoma (LAHNSCC) have inherent biases like biological and temporal selection. Our study considered all patients deemed fit for salvage surgery and compared to those who underwent surgery versus those who refused it thus throwing light on the real world benefit of salvage surgery. METHODS: This was a post hoc analysis of a phase 3 randomized trial conducted between 2012 and 2018. Out of 536 LAHNSCC patients randomised in the study, 113 patients had residual disease or recurrent disease and were planned for salvage surgery in a multidisciplinary clinic. Patients were divided into 2 cohorts for comparison, willing for salvage surgery (n = 91) and unwilling for salvage surgery(n = 22). The primary endpoint was overall survival. RESULTS: The median follow up was 28.7 months (95%CI 23.9-33.5 months). Out of the 91 patients who were willing for salvage surgery, 78 underwent same. The median survival in cohort of patients willing for salvage surgery was 22.0 months (95%CI 10.1-33.9) while it was 9.7 months (95%CI 6.6-12.8) in patients who were unwilling for salvage surgery (HR = 0.262 95%CI HR 0.147-0.469, p = 0.000). CONCLUSION: Salvage surgery leads to a substantial improvement in outcomes in head and neck cancers and should be the de facto standard of care in patients who are eligible for the same.


Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Terapia de Salvação/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Adulto , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Taxa de Sobrevida/tendências , Resultado do Tratamento
8.
South Asian J Cancer ; 9(1): 47-49, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31956622

RESUMO

INTRODUCTION: The treatment of lung cancer is not defined in the third-line setting and remains an unanswered question. Erlotinib is the only drug approved in the third-line setting. With the introduction of effective first- and second-line therapies, more and more patients warrant an effective third-line therapy. We did a post hoc analysis of our randomized trial for the epidermal growth factor receptor (EGFR)-positive patients who received third-line therapy. MATERIALS AND METHODS: The present series is of 85 patients who received third-line therapy. Demographic data were collected which included age, performance status, gender, stage, comorbidities, and sites of metastasis. Data were collected for the type of systemic treatment patients received and number of cycles received. Information related to the impact of treatment on the symptoms of patients and the imaging done for response evaluation was collected. RESULTS: Of the 85 patients, there were 13 patients (15%) who achieved a partial response and 34 patients (40%) who had stable disease as best response. There were no complete response and 20 patients (24%) had disease progression at the time of first assessment. The median overall survival (OS) was 8.36 months (95% confidence interval [CI] 6.8-9.8 months) and median progression-free survival was 4.4 months (95% CI 3.3-4.9 months). Grade 3 or 4 toxicities were seen in 42.5% (n = 36) of the total patients. CONCLUSIONS: The study provides the patterns and outcomes of systemic treatment in metastatic EGFR-mutated lung adenocarcinoma in patients who have progressed on two or more lines of systemic therapies. This data suggest that third-line systemic therapy may provide meaningful outcomes in these patients.

13.
South Asian J Cancer ; 8(3): 173-177, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489292

RESUMO

Introduction: Nasopharyngeal carcinoma is a rare malignancy. We conducted an audit of systemic therapies received in palliative setting in carcinoma nasopharynx and studied their outcomes. Methods: Patients who underwent first-line palliative systemic chemotherapy between January 2014 and April 2017 for carcinoma nasopharynx at the department of medical oncology at authors' institute were selected for this analysis. Toxicities, responses, progression-free survival (PFS), and overall survival (OS) were analyzed. In addition, a Quality-Adjusted Time without Symptoms or Toxicity analysis with threshold utility analysis was performed. Results: Fifty-one patients were included in this analysis. The indication of palliative chemotherapy was locoregionally recurrent disease in 25 (49.0%) patients and metastatic disease in 26 (51.0%) patients. The overall response rate was 62.0% (n = 33). The median PFS was 225 days (95% confidence interval [CI]: 164-274 days) and median OS was 513 days (95% CI: 286-931 days). The restricted mean TOX state duration was 2.6 days (95% CI: 0.3-4.9), restricted mean TWiST duration was 219.2 days (95% CI: 184.0-254.4), and restricted mean REL duration was 74.3 days (95% CI: 38.1-110.4). Conclusion: Systemic cytotoxic therapy in nasopharyngeal cancers is associated with high response rates and clinically meaningful PFS; with low duration of time spent in adverse events.

14.
J Clin Oncol ; 37(32): 3032-3041, 2019 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-31539316

RESUMO

PURPOSE: Platinum-resistant oral cancer has a dismal outcome with limited treatment options. We conducted a phase I/II study to identify the optimal biologic dose (OBD) of methotrexate when given along with erlotinib and celecoxib and to assess the efficacy of this three-drug regimen in advanced oral cancer. METHODS: Patients with platinum-resistant or early-failure squamous cell carcinoma of the oral cavity were eligible for this study. They were orally administered erlotinib 150 mg once per day, celecoxib 200 mg twice per day, and methotrexate per week. The primary end point of phase I was to determine the OBD of methotrexate, and that of phase II was to determine the 3-month progression-free survival. The OBD of methotrexate was determined on the basis of the clinical benefit rate at 2 months and circulating endothelial cell level at day 8, using a de-escalation model. Pharmacokinetic evaluation was performed during phase I. Phase II consisted of an expansion cohort of 76 patients. RESULTS: Fifteen patients were recruited in phase I, and 9 mg/m2 methotrexate was identified as the OBD. A total of 91 patients were recruited, and the median follow-up was 6.8 months (range, 0 to 16.8 months). The 3-month progression-free survival rate was 71.1% (95% CI, 60.5% to 79.3%), the 6-month overall survival rate was 61.2% (95% CI, 49.2% to 67.8%), and the response rate was 42.9% (95% CI, 33.2% to 53.1%; n = 39). The mean Functional Assessment of Cancer Therapy-Head and Neck Trial Outcome Index score at day 8 was improved by 6.1 units (standard deviation, 13.6 units) and was maintained around this magnitude (P = .001). CONCLUSION: Triple oral metronomic chemotherapy with erlotinib, methotrexate, and celecoxib is efficacious in platinum-refractory oral cavity cancers and represents a new therapeutic option in patients with poor prognosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Bucais/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Administração Metronômica , Adulto , Idoso , Celecoxib/administração & dosagem , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Cloridrato de Erlotinib/administração & dosagem , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Compostos Organoplatínicos/farmacologia , Intervalo Livre de Progressão
15.
Cancer ; 125(18): 3184-3197, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31150120

RESUMO

BACKGROUND: Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to confirm these findings. METHODS: This open-label, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2 ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT).The primary endpoint was progression-free survival (PFS); key secondary endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent-to-treat analysis also was performed. RESULTS: In total, 536 patients were allocated equally to both treatment arms. The median follow-up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio [HR], 0.69; 95% CI, 0.53-0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50-0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55-0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65-1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01). CONCLUSIONS: The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3-weekly schedule of 100 mg/m2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos/uso terapêutico , Quimiorradioterapia/métodos , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosite/etiologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Trombocitopenia/etiologia , Adulto Jovem
16.
South Asian J Cancer ; 7(4): 249-253, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30430094

RESUMO

Background: Quality-adjusted time without toxicity (Q-TWiST) and quality of life (QOL) are indicators of benefit provided by different chemotherapy regimens. Methods: This was a prospective study, in which adult head-and-neck (H and N) cancer patients, treated with metronomic chemotherapy were enrolled. The Functional Assessment of Cancer Therapy-General H and N (FACT-G and H and N) version 4 pro formas were self-administered before the start of chemotherapy and then at 2, 4, and 6 months. FACT QOL and Q-TWiST analysis were then performed. Results: There was an improvement in the social well-being (P = 0.370), emotional well-being (P = 0.000), functional well-being (P = 0.000), H and N cancer subscale (P = 0.001), FACT H and N trial outcome index (P = 0.000), FACT G-total score (P = 0.000), and FACT H and N total score (P = 0.000) with palliative chemotherapy. The QTWiST value for a utility score of 0.25 for toxicity and relapse state was 145.93 days. Conclusion: Metronomic chemotherapy is associated with improvement in QOL and has a low duration of time spent in toxicity state.

17.
J Glob Oncol ; 4: 1-10, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30241232

RESUMO

PURPOSE: This study reports the incidence of distress, the factors associated with distress, and a practical strategy to resolve distress in patients with head and neck cancer who are starting palliative chemotherapy. METHODS: Adult patients with head and neck cancer planned for palliative chemotherapy underwent distress screening before the start of treatment as part of this single-arm prospective study. Patients who had a distress score > 3 on the National Comprehensive Cancer Network (NCCN) distress thermometer were counseled initially by the clinician. Those who continued to have high distress after the clinician-led counseling were referred to a clinical psychologist and were started on palliative chemotherapy. After counseling, distress was measured again. The relation between baseline distress and compliance was tested using Fisher's exact test. RESULTS: Two hundred patients were enrolled, and the number of patients with high distress was 89 (44.5% [95% CI, 37.8% to 51.4%]). The number of patients who had a decrease in distress after clinician-led counseling (n = 88) was 52 (59.1% [95% CI, 48.6% to 68.8%]) and after psychologist-led counseling (n = 32) was 24 (75.0% [95% CI, 57.6% to 72.2%]; P = .136). Compliance rates did not differ between the patients with or without a high level of distress at baseline (74.2% v 77.4%, P = .620). CONCLUSION: The incidence of baseline distress is high in patients awaiting the start of palliative chemotherapy. It can be resolved in a substantial number of patients using the strategy of clinician-led counseling, with additional referral to a clinical psychologist as required. Patients with a greater number of emotional problems usually require psychologist-led counseling.


Assuntos
Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/psicologia , Estresse Psicológico/terapia , Idoso , Feminino , Humanos , Masculino , Cuidados Paliativos , Cooperação do Paciente
18.
J Glob Oncol ; 4: 1-10, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30241240

RESUMO

PURPOSE: Metastatic osteosarcoma is largely treated with high-dose methotrexate (HDMTX)-based therapy, especially in the pediatric population. This mandates complex pharmacokinetic monitoring in a costly inpatient setting to mitigate unpredictable serious toxicities. Hence, a non-HDMTX-based regimen is worth exploring, especially in India and low- and middle-income countries. MATERIALS AND METHODS: All consecutive treatment-naïve patients with metastatic osteosarcoma were prospectively treated on the novel OGS-12 protocol consisting of sequential doublets of doxorubicin, cisplatin, and ifosfamide. Four cycles were administered as neoadjuvant therapy followed by planned curative intent surgery and metastasectomy when feasible, followed by four cycles of adjuvant chemotherapy. Baseline characteristics, histologic response, event-free survival (EFS), overall survival (OS), and toxicity data were prospectively collected. RESULTS: Three hundred seventeen patients were enrolled onto the OGS-12 protocol from 2011 to 2014, of whom 80 (25%) had metastatic disease; median age was 17 years. The majority of patients were nutritionally challenged with high-risk features. At presentation, 83% of patients (66 patients) had lung metastases. After neoadjuvant chemotherapy, 57% of patients were histologically good responders. Four-year EFS and OS rates were 24% and 27%, respectively, in the intent-to-treat population and 27% and 29%, respectively, in the per-protocol analysis. Significant grade 3 or 4 toxicities were febrile neutropenia (51%), thrombocytopenia (36%), and anemia (54%). Histologic response was an independent predictor for EFS and OS in patients who underwent surgery. Surgical intervention was found to be significant for survival in univariable analysis. CONCLUSION: The novel, low-cost, non-HDMTX-based, dose-dense OGS-12 regimen has shown comparable outcomes to international standards in metastatic osteosarcomas and is worthy of wider clinical application. An aggressive multimodality approach may result in long-term survival in a select group of patients and, hence, is worth considering.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Metotrexato/uso terapêutico , Osteossarcoma/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Criança , Feminino , Humanos , Masculino , Metotrexato/farmacologia , Pessoa de Meia-Idade , Metástase Neoplásica , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Atenção Terciária à Saúde , Resultado do Tratamento , Adulto Jovem
20.
Lung India ; 35(1): 27-30, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29319030

RESUMO

BACKGROUND: This study was designed to evaluate the differential effect of epidermal growth factor receptor (EGFR) mutation status (exon 19 vs. 21) on progression-free survival (PFS) and overall survival (OS) in treatment-naïve advanced EGFR mutation-positive nonsmall cell lung cancer (NSCLC) treated with gefitinib as first-line agent. METHODS: This was a post hoc analysis of EGFR-mutated (exon 19 and 21) advanced-stage (Stage IIIB or IV), chemotherapy-naive NSCLC patients treated with gefitinib as first line in a phase 3 randomized study. Patients were treated with gefitinib 250 mg daily. Patients underwent axial imaging for response assessment on D42, D84, D126, and subsequently every 2 months till progression. Responding or stable patients were treated until progression or unacceptable toxicity. SPSS was used for statistical analysis. Kaplan-Meier method was used for survival estimation and log-rank test for comparison. Cox proportion hazard model was used for multivariate analysis. RESULTS: One hundred and forty-one patients were eligible for analysis, of which 78 were males and 63 were females. A total of 127 patients (90.1%) were ECOG 0-1 while 14 patients (9.1%) were ECOG >1. Exon 21 mutation was present in 65 patients (46.1%) and exon 19 mutation in 76 patients (53.9%). One hundred and thirty-three of 141 patients were evaluable for response. Response rate of patients having exon 19 mutation was 72.9% (51 patients, n = 70) while it was 55.6% in patients having exon 21 mutation (35 patients, n = 63) (P = 0.046). Median PFS in exon 19-mutated patients was 9.3 months (95% confidence interval [CI] 6.832-11.768) compared to 7.8 months (95% CI 5.543-10.0) (P = 0.699) in exon 21-mutated patients. The median OS in exon 19-mutated patients was 19.8 months (95% CI 16.8-22.7), and it was 16.5 months (95% CI 10.9-22.1) in exon 21-mutated patients (P = 0.215). CONCLUSION: There were no differential outcomes in the Indian patients of advanced-stage NSCLC with exon 19 and 21 EGFR mutations treated with gefitinib.

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