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Shivaani Kummar

Publications and source records attributed to Shivaani Kummar.

14 recordsLinked to original sources
PubMed2026

Larotrectinib in TRK fusion differentiated thyroid carcinoma: updated trial data.

Larotrectinib is a first-in-class, highly selective, central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for tumour-agnostic use in TRK fusion cancer. It has previously demonstrated rapid and durable disease control and favourable safety in patients with advanced TRK fusion thyroid carcinoma (TC). After an additional 4 years of follow-up with the inclusion of two additional patients, and utilising an independent review committee (IRC) to assess overall response rate (ORR), we report updated pooled analyses from three phase 1-2 larotrectinib clinical trials, focusing only on patients with TRK fusion differentiated TC (DTC). The primary endpoint was the IRC-determined ORR per RECIST v1.1. Duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety were also assessed. Twenty-four patients (papillary TC, n = 21; follicular TC, n = 2; poorly DTC, n = 1) were included (data cut-off: 20 July 2024). ORR was 79% (95% confidence interval (CI): 58-93); best responses were complete response in 3 (13%) patients, partial response in 16 (67%), stable disease in 3 (13%), progressive disease in 1 (4%) and not evaluable in 1 (4%). Median DoR and PFS were 35 (95% CI: 22-not estimable (NE)) and 44 (95% CI: 35-NE) months, respectively; 6-year OS rate was 71% (95% CI: 50-91). Six patients remained on treatment. Treatment-related adverse events (TRAEs) were mainly grade 1/2; no patients permanently discontinued treatment due to TRAEs. Larotrectinib continues to demonstrate durable disease control, extended survival and a favourable long-term safety profile in patients with advanced TRK fusion DTC requiring systemic therapy.

Humans↗
PubMed2006

Targeting epigenetic abnormalities with histone deacetylase inhibitors.

BACKGROUND: Alterations in chromosome structure play critical roles in the control of gene transcription. These "epigenetic" alterations include modification of histones and other proteins by acetylation and/or phosphorylation. Normally, these modifications are balanced finely and are highly reversible in normal tissues, but they may be imbalanced and heritable in tumor cells. Histone deacetylase inhibitors increase histone acetylation, thereby modulating the expression of a subset of genes in a coordinated fashion. Several tumor suppressor genes associated with the malignant phenotype are repressed by epigenetic mechanisms in sporadic cancers. Thus, therapy with histone deacetylase inhibitors may alter tumor phenotype to inhibit growth in such tumors. METHODS: The authors reviewed the rationale for histone deacetylase inhibitors as potential anticancer agents and reviewed some preclinical and early clinical trial data with various classes of histone deacetylase inhibitors. RESULTS: Preclinical and clinical antitumor activity has been observed. Toxicities include fatigue, myelosuppression, and cardiac abnormalities. CONCLUSIONS: Histone deacetylase inhibitors have shown promising activity in some solid tumors and hematologic malignancies.

Acetylation↗
PubMed2006

Drug development in oncology: classical cytotoxics and molecularly targeted agents.

There is an apparent need to improve the speed and efficiency of oncological drug development. Furthermore, strategies traditionally applied to the development of standard cytotoxic chemotherapy may not be appropriate for molecularly targeted agents. This is particularly the case for exploratory Phase 1 and 2 trials. Conventional approaches to determine dose based on maximum tolerability and efficacy based on objective tumour response may not be suitable for targeted agents, since many of them have a wide therapeutic index and inhibit tumour growth without demonstrable cytotoxicity. Instead, exploratory trials of targeted agents may have to focus on other end-points such as pharmacological effects and disease stabilization. Thus, there is an increasing interest in making the best possible use of biomarkers and pharmacogenomics in early phases of drug development.

Antineoplastic Agents↗
PubMed2005

Determination of the heat shock protein 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin in plasma by liquid chromatography-electrospray mass spectrometry.

A rapid method was developed for the quantitative determination of the novel heat shock protein 90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG; NSC707545), in human plasma. Calibration curves were constructed, and were analyzed using a weight factor proportional to the nominal concentration. Sample pretreatment involved a one-step extraction with ethyl acetate of 0.5-ml samples. The analysis was performed in the range of 1-100 ng/ml on a column (75 mm x 2.1 mm internal diameter with 3.5 microm C18 particle size), using 55% methanol in water containing formic acid as the mobile phase. The column effluent was monitored by mass spectrometry with positive electrospray ionization. The values for precision and accuracy were always <8% and <10% relative error, respectively. The method was successfully applied to examine the pharmacokinetics of 17-DMAG in a cancer patient.

Benzoquinones↗
PubMed2005

Non-small-cell lung cancer vaccine therapy: a concise review.

Lung cancer is the leading cause of cancer deaths in the United States and throughout the world; globally, there are more than 1.1 million deaths each year. Treatment modalities currently employed are significantly limited; 50% of patients experience disease recurrence after surgery, and less than a quarter of patients respond to systemic chemotherapy. These statistics have fueled the search for a safer, more effective treatment modality. Despite significant advances in our understanding of the molecular basis of cancer immunology, many obstacles remain. However, encouraging clinical results in patients immunized with autologous tumor cell vaccines expressing granulocyte macrophage colony-stimulating factor strongly advocate further investigation of immunotherapy in non-small-cell lung cancer (NSCLC). Further studies are needed to demonstrate whether these novel therapies can potentially complement or even replace current therapeutic approaches. We present a review of the various vaccine-based strategies employed to target and treat NSCLC.

Animals↗
PubMed2005

A phase I and pharmacokinetic study of VNP40101M, a new alkylating agent, in patients with advanced or metastatic cancer.

PURPOSE: VNP40101M is a new alkylating agent that demonstrated broad anti-tumor activity in murine tumor models. A phase I trial was initiated to determine the toxicities, maximum tolerated dose, and pharmacokinetics of VNP40101M by short IV infusion. STUDY DESIGN: The starting dose was 3 mg/m(2) every four weeks, and was escalated in successive cohorts as follows: 6, 12, 24, 40, 60, 80, and 100 mg/m(2). Beyond 100 mg/m(2), dose increments were 25%. Initially, 1-2 patients were assigned to a dose level. Intra-patient dose escalation was permitted. With the first instance of a drug-related > or = grade 2 adverse event, all dose levels required assessment of 3-6 patients. Pharmacokinetic parameters were assessed in the first cycle and any cycle with a change in dose. RESULTS: Twenty-six patients in 13 dose levels ranging from 3-305 mg/m(2) were evaluated. Dose-related thrombocytopenia was the major toxicity, with the nadir occurring at a median of day 27. At 305 mg/m(2), six of eight patients developed grade 3 thrombocytopenia, including one event that met the definition for DLT. Other dose-related toxicities included moderate granulocytopenia, anemia, and a mild infusion-related syndrome consisting of acute headache and facial flushing. The granulocyte nadir occurred at a median of day 34, and recovery of both thrombocytopenia and neutropenia to < grade 2 occurred at a median of day 43. VNP40101M peak plasma concentrations and AUC were linear with dose. The elimination half-life was short and estimated to be approximately 15 minutes. CONCLUSIONS: The MTD and recommended dose for phase II trials is 305 mg/m(2) every six weeks. Phase II trials in less heavily pre-treated patient populations are warranted.

Adult↗
PubMed2005

Establishing a platform for immunotherapy: clinical outcome and study of immune reconstitution after high-dose chemotherapy with progenitor cell support in breast cancer patients.

Tumor vaccine after high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) aims at directing immune recovery toward tumor responses after optimizing minimal residual disease. We have characterized T-cell recovery and tumor response after a regimen devised as a platform for such immunotherapy. One hundred patients with high-risk or metastatic breast cancer received 3 to 7 cycles of paclitaxel and cyclophosphamide (overall response rate, 78%) and then HDC with melphalan and etoposide. Seventy-one patients received HDC and ASCT (no mortality at 100 days). At 24 months after transplantation, progression-free and overall survival probabilities for patients with stage IIIA, IIIB, and IV disease were 82%, 81%, and 42% and 100%, 94%, and 68%, respectively. The median progression-free and overall survivals from entry on study for stage IV patients were 15.3 and 38.1 months, respectively. CD3 + , CD8 + , and CD4 + cells were severely depleted after ASCT. Although total CD8 + T-cell numbers approached the normal range by 3 months, most of these cells were CD28 - . Naive CD45RA + CD4 + T cells approached the normal range only 18 months after ASCT and only in younger patients. The described observations provide the basis for devising a strategy for cancer vaccine administration after ASCT. Incorporating immune reconstitution enhancement after ASCT may be advantageous.

Adult↗
PubMed2005

Primary non-Hodgkin's lymphoma of the liver.

We review the literature on primary hepatic lymphoma (PHL). PHL is a rare malignancy, and constitutes about 0.016% of all cases of non-Hodgkin's lymphoma. It has been reported to occur with increased frequency in patients with chronic hepatitis C infection. Most patients with PHL present with abdominal pain, constitutional symptoms and have hepatomegaly on examination. Imaging studies reveal solitary, or less often, multiple masses in the liver. The predominant histology is B-cell lymphoma, most commonly diffuse large cell type. Most patients are treated with chemotherapy, with some physicians employing a multimodality approach incorporating surgery and radiotherapy with chemotherapy. The prognosis is variable, with good response to early aggressive combination chemotherapy.

B-Lymphocytes↗
PubMed2003

Unusual sites of colorectal cancer metastasis.

We present 2 separate cases of adenocarcinoma of the colon with metastasis to the chin and the bladder, both of which are unusual sites of colorectal cancer metastasis. Patient 1 is a 77-year-old man who was diagnosed with adenocarcinoma of the colon, American Joint Committee on Cancer (AJCC) T4 N0 M0 (stage II), and underwent a right hemicolectomy. Fourteen months later he developed a firm 2.5-cm mass involving the chin. Excisional biopsy revealed moderately differentiated adenocarcinoma, consistent with the known colon primary tumor. Patient 2 is a 75-year-old man who was diagnosed with AJCC T3 N1 M0 (stage III) adenocarcinoma of the colon and underwent sigmoid colectomy. Ten years later, he was found to have transitional cell carcinoma involving retroperitoneal nodes with no identifiable bladder or ureteral primary, for which he received chemotherapy. Eighteen months following this diagnosis, he developed hematuria and was found to have metastatic colon adenocarcinoma involving the bladder. Details of both patient cases are presented here.

Adenocarcinoma↗
PubMed2002

Management of small bowel adenocarcinoma.

Small bowel adenocarcinoma is a relatively rare malignancy. Only limited information is available on the incidence, prognosis, and role of chemotherapy in the treatment of this disease. We present a review of currently available clinical data to assist the practicing oncologist in the treatment of these patients. Approximately 5,300 new cases and 1,100 deaths from small bowel adenocarcinoma are reported annually in the United States. Increased incidence is seen in patients with Crohn's disease, hereditary nonpolyposis colorectal cancer, and familial adenomatouspolyposis. Factors associated with poor prognosis are age > 75 years, lack of surgical resection, advanced stage, and tumor arising in the duodenum. The median survival of patients with localized, locally advanced, and metastatic disease is 50.1, 22.2, and 8.6 months, respectively. Few data exist on the use of (neo)adjuvant or palliative chemo(radio)therapy in this setting. Fluorouracil (5-FU)based chemotherapy, as a single agent or in combination with others, has been used in most case series. Duodenal adenocarcinoma accounts for more than 50% of all cases of small bowel adenocarcinoma. Resectability is the key prognostic factor, along with age, performance status, tumor location, and presence of distant metastasis. Although the activity of 5-FU-based regimens has been documented, the assessment of clinical benefit is hindered by the lack of prospective, randomized data.

Adenocarcinoma↗