Nivolumab in Recurrent/Metastatic Squamous Cell Carcinoma of Head and Neck: A Tertiary Cancer Center Experience.

Apurva A. PatelAnanya PareekBackground Immunotherapy is a proven therapeutic option in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum therapy. At present, there are no published Indian data regarding administration of nivolumab in this setting. Aim The aim of this study is to retrospectively evaluate the efficacy and toxicity of nivolumab in R/M HNSCC among Indian patients who progressed after one or more lines of chemotherapy, including platinum agents. Methods All patients of R/M HNSCC who received nivolumab between 2/6/2018 to 31/3/2020 were assessed retrospectively for the efficacy and toxicity of nivolumab therapy. Statistical Analysis All the data analysis was performed using IBM SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, N.Y., USA). Descriptive analysis was performed to obtain baseline characteristic of the study sample. Survival analysis was done using the Kaplan-Meier method. Results Nivolumab therapy was tolerated well, with no new safety concerns, except one (8.3%) patient experienced grade ¾ toxicity (gastrointestinal). The clinical benefit rate (CBR) was found to be 66.7%. The median progression-free survival (PFS) was 3 months (95% CI; 2.093-3.907), and median overall survival (OS) was 8 months (95% CI; 3.731-12.269) from the date of first dose of nivolumab. Conclusions In our study, efficacy and toxicity were comparable with international data with no new safety concerns. Nivolumab emerged as an astonishing treatment option with tolerable toxicity profile in patients with R/M HNSCC postplatinum therapy, although limited treatment options are available at present.

Fixed dose combination of capecitabine and cyclophosphamide in metastatic breast cancer: Results from THE ENCLOSE phase 2/3 randomized multicenter study.

AIM: To evaluate pharmacokinetics, efficacy and safety of fixed-dose combination (FDC) of oral capecitabine + cyclophosphamide in metastatic breast cancer (MBC) patients progressing after anthracycline and/or taxane chemotherapy. METHODS: In this prospective, adaptive, phase-2/3, open-label study (CTRI/2014/12/005234), patients were randomized (1:1:1) to three FDC doses (doses/day: D1, capecitabine + cyclophosphamide 1400 mg + 60 mg; D2, 1800 mg + 80 mg; D3, 2200 mg + 100 mg) for 14 days, in 21-day cycles. In Part-I, multiple-dose pharmacokinetics and optimal dose(s) were evaluated with futility analysis. Group(s) with <3 responders based on best overall response rate (BOR, complete response [CR]+partial response [PR]), were discontinued. Efficacy (BOR, disease control rates [DCR; CR + PR + stable disease]) and safety of optimal dose(s) were evaluated in Part-II. RESULTS: Of 66 patients (n = 22/group) in Part-I, pharmacokinetics (D1 = 7/22, D2 = 9/22, D3 = 8/22) showed dose-proportionality for cyclophosphamide and greater than dose-proportionality for capecitabine. Modified intent-to-treat (mITT) analysis showed BOR of 7.14% (1/14) in D1 (discontinued), and 22.22% (4/18) each in D2 and D3, respectively. In Part-II, 50 additional patients were randomized in D2 and D3 (n = 144; total 72 [22 + 50] patients/group). mITT analysis in D2 (n = 54) and D3 (n = 58) showed BOR of 29.63% (16/54, 95%CI: 17.45-41.81%) and 22.41% (13/58, 95%CI: 11.68-33.15%), respectively. DCR in D2 and D3 were 87.04% (47/54, 95%CI: 78.08-96.00%) and 82.76% (48/58; 95%CI: 73.04-92.48%) after 3 and 57.41% (31/54; 95%CI: 52.41-79.50%) and 50.00% (29/58; 95%CI: 40.40-67.00%), after 6-cycles, respectively. Hand-foot syndrome (16.67%), vomiting (9.72%) in D2, and hand-foot syndrome (18.06%), asthenia (15.28%) in D3 were most-common adverse events. CONCLUSION: FDC of capecitabine + cyclophosphamide (1800 + 80 mg/day) showed high disease control rates and good safety profile in MBC patients.

Impact of nationwide lockdown on cancer care during COVID-19 pandemic: A retrospective analysis from western India.

BACKGROUND AND AIMS: COVID-19 has impacted healthcare system worldwide including cancer case. Aim of this study was to describe the experience of lockdown on cancer care concerning patient's visit and reception of treatment in western India. METHODS: This is a retrospective observational study conducted in patients with cancer attending a tertiary care center pre-lockdown and during lockdown (from January to May 2020). Data related to demographic parameters, type of tumor, type of treatment received and functional status of patients were retrieved from hospital medical records of patients. RESULTS: Of the 5258 patients included, 4363 visited hospital pre-lockdown (median age, 50 years) and 895 visited during the lockdown period (median age, 47 years). A total of 1168 and 106 patients visiting hospital before and during lockdown, respectively, had comorbidities. Breast cancer (25.6% and 29.7%), head and neck cancer (21.3% and 16.9%) were the most common type of solid tumors; leukemia (58.0% and 73.0%), lymphoma (18.8% and 13.5%) and multiple myeloma (18.6% and 12.2%) were the most common type of hematological malignancies observed in patients visiting pre-lockdown and during lockdown, respectively. Chemotherapy was most commonly received treatment (pre-lockdown, 71.8%; during lockdown, 45.9%). Other therapies reported includes supportive/palliative, targeted, hormonal, and immunotherapy. The majority of patients who visited the hospital pre-lockdown (68.4%) and during lockdown (62.8%) had 0 or 1 Eastern Cooperative Oncology Group (ECOG) score. CONCLUSION: Overall observations highlight a substantial impact of an imposed nationwide lockdown during COVID-19 pandemic on cancer care of patients in terms of reduced patient visits and number of treatments received.

Clinical and epidemiological profile of neuroendocrine tumors: An experience from a regional cancer center from Western India.

BACKGROUND: Most of the data on neuroendocrine tumors (NETs) are from the Western literature. Indian studies regarding clinicopathological characteristics and treatment outcomes are lacking. METHODS: This is a prospective observational study of all new patients with NETs (except small-cell lung cancer) registered at our tertiary care cancer institute from November 2014 to November 2016. A total of 97 new patients were registered, of which 20 were lost to follow-up before starting any planned treatment. Epidemiological and clinicopathological features of all these 97 patients were studied, and the remaining 77 patients were analyzed for treatment response and survival analysis. RESULTS: The median age at diagnosis was 49 years (20-74 years) with male preponderance (M: F = 1.85:1). The most common primary site of origin was pancreas (34/97 = 35%), followed by unknown primary origin (19%), small intestine (9%), and pulmonary (6%). Of 97 patients, 91 (93.8%) presented with nonfunctional symptoms, 3 (3.1%) had purely functional symptoms, and 3 (3.1%) presented with both functional and nonfunctional symptoms. The most common presenting symptom was abdominal pain (59.7%), followed by jaundice (9.3%), whereas watery diarrhea (83.3%) and flushing (66.7%) were the most common functional symptoms. Sixty-six percent (64/97) of cases were metastatic at presentation. A strong correlation was noted between the primary site of origin and metastatic presentation (P = 0.016). Chemotherapy was the most common primary therapy (40.2%), followed by surgery (28.6%), watchful waiting (15.6%), and somatostatin analogs (11.7%). The median event-free survival was highest for patients undergoing surgery (10 months). CONCLUSIONS: The clinicopathological profile of NETs in the Indian population differs from Western countries. Majority of patients present with metastatic disease, thus representing a need for creating awareness among patients and medical fraternity and formulating Indian guidelines for optimized treatment.

Hemangiopericytoma of supraglottis: A rare case report and review of literature.

In 1942, Stout and Murray first used the term hemangiopericytoma to describe a tumor which is distinguished histologically from other types of vascular neoplasm characterized by proliferation of pericytes. It is a rare neoplasm that was originally described as a vascular tumor derived from the pericytes. They account for 2%-3% of all soft tissue sarcomas in humans and they occur mainly in the musculoskeletal system. About 15%-30% of all hemangiopericytomas occur in the head and neck region. Hemangiopericytoma of supraglottis is very rare neoplasm with only nine cases reported in literature and ours is the tenth case overall and first case in pediatric age group. Herein, we are presenting an extremely rare case report of hemangiopericytoma of supraglottis in a 6-year-old male child who presented with stridor followed by which tracheostomy was done. Later, the patient was treated initially with radiotherapy followed by surgery, i.e., laryngectomy in view of residual disease postcurative radiotherapy. Hence, hemangiopericytoma is a very rare tumor overall and can present in pediatric age group and can be one most important differential diagnosis because many patients in this age group, stridor most commonly occurs due to the infectious causes such as influenza virus and diphtheria-induced croup, i.e., laryngotracheobronchitis.

Rare occurrence of hand-foot syndrome due to paclitaxel: A rare case report.

Hand-foot syndrome (HFS) is a relatively frequent adverse reaction to certain anticancer drugs. HFS is a type of dermatitis which has been most commonly described with 5-fluorouracil and capecitabine. However, HFS with paclitaxel is rare and has been reported sparingly in the literature. A 52-year-old male patient with recurrent carcinoma of the buccal mucosa was started on palliative chemotherapy regimen, injection paclitaxel (175 mg/m2) in combination with injection carboplatin. On post-chemotherapy day 13, the patient started developing pain, dysesthesia followed by bullae formation, and desquamation over palms and soles. Clinically, the patient had Grade 3 HFS characterized by symmetrical, tender skin lesions over the dorsal aspect of palms, and soles with desquamation necessitating interruption of treatment. Therefore, this case has been presented to be cognizant with this rare form of side effect with one of the most commonly used drug in oncology.

Solitary Plasmacytoma of Bone Involving Spine in a 12-year-old Boy: Report of a Rare Case and Review of Literature.

Solitary plasmacytoma of the bone (SPB) is a rare plasma cell neoplasm representing only about 5% of plasma cell neoplasia. It usually presents as a lytic lesion mainly localized within the axial skeleton. SPB is exceedingly rare in young individuals, and only few cases have been reported so far in patients younger than 20 years of age. In view of rarity of disease, definitive treatment guidelines have not been established. We hereby report a case of SPB involving of lumbar vertebra (L5) in a 12-year-old boy. He was initially treated with antilymphoma therapy and curative radiotherapy considering as primary bone lymphoma. However, he had local recurrence with paraparesis after 9 months which was diagnosed as solitary bone plasmacytoma for which he was treated with decompressive laminectomy and chemotherapy (bortezomib, lenalidomide, and dexamethasone). The purpose of this article is to report a rare case of SPB in a pediatric patient and to review the available literature and treatment options. SPB should be considered in the differential diagnosis of osteolytic bone lesions even in young patients.

Ifosfamide-induced Encephalopathy Precipitated by Aprepitant: A Rarely Manifested Side Effect of Drug Interaction.

Central nervous system (CNS) toxicity has been reported in approximately 10%-30% of patients receiving intravenous infusions of ifosfamide. Encephalopathy is a rare but serious CNS adverse reaction in these patients, and although usually transient and reversible, may cause persistent neurological dysfunction or death. Clinical features range from fatigue and confusion to coma and death. Ifosfamide forms backbone of various treatment regimens including curative treatment and palliative chemotherapy regimen. Precipitation of ifosfamide-induced encephalopathy (IIE) by aprepitant has been reported in the literature rarely. Ifosfamide is moderately emetogenic; hence, aprepitant is used to prevent emesis induced by ifosfamide. We here report a case where a patient of recurrent B-cell Philadelphia-negative acute lymphoblastic lymphoma was given aprepitant to prevent ifosfamide-induced emesis. After 24 h of ifosfamide infusion, the patient developed symptoms of encephalopathy, i.e., headache, vomiting, and one episode of seizure which was followed by disoriented behavior. After doing all routine investigations and neuroimaging, the diagnosis of IIE was kept on clinical grounds, and after looking for the various factors, we came across injection fosaprepitant as the precipitating factor. On the clinical grounds, the patient was treated with hydration and injection methylene blue for above complaints, and the patient recovered without any residual deficit within 48-72 h. Hence, in the presence of causative agent, i.e., ifosfamide and precipitating agent injection fosaprepitant with negative imaging and normal laboratory parameters as well as the early and good response to methylene blue, the diagnosis of IIE precipitated by aprepitant was confirmed.

Safety and Efficacy of Eltrombopag in Post-hematopoietic Stem Cell Transplantation (HSCT) Thrombocytopenia.

Twelve adult patients (median age 29.5 years) were started on Eltrombopag 25-50 mg/day for post-hematopoietic stem cell transplantation (HSCT) thrombocytopenia. All patients were having primary thrombocytopenia after HSCT. No patient had other secondary cause for thrombocytopenia. Two patients were allogenic subsets (1 acute myeloid leukemia i.e., AML and 1 aplastic anemia), and 10 were autologous transplants (3 multiple myeloma, 6 lymphoma and 1 AML). Nine patients were males, three were females. The median time of starting Eltrombopag was 21 days post-stem cell infusion (range day +17 to +60) at a median platelet count of 9,000/cmm (range 3,000-11,000/cmm). The median duration for treatment was 29 days. Median total dose of 812.5 mg was received by patients and they had a median platelet increment of 36,000/cmm. We observed that there were no adverse effects in these patients and there was a gradual increase in platelet count so that none of the patients had any complication due to thrombocytopenia. The cost of treatment was less than the cost of extended hospitalization and irradiated single donor platelet transfusion.

Improving Outcome of Aplastic Anaemia with HLA-Matched Sibling Donor Hematopoietic Stem Cell Transplantation: An Experience of Gujarat Cancer and Research Institute (GCRI).

Fifteen patients, with a median age of 19 years having severe aplastic anaemia (SAA) underwent human leucocyte antigen (HLA) identical sibling donor hematopoietic stem cell transplantation (HSCT) using conditioning regimens containing cyclophosphamide with antithymocyte globulin (ATG) or a combination of fludarabine and cyclophosphamide with or without ATG during December 2007 to May 2013. Cyclosporine and mini methotrexate were used as graft versus host disease (GVHD) prophylaxis. Graft source included peripheral blood stem cells in 11, bone marrow in 3 and both in 1. One patient had primary graft failure while 14 patients were engrafted with a median neutrophil and platelet engraftment time of 13.5 days. One patient had secondary graft rejection. Acute GVHD occurred in 3 patients and chronic GVHD in 4. One year death rate in engrafted patients was 14.28 %. At a mean follow-up of 21.2 months, 12 (80 %) are alive and well. One of the donors was a patient of haemophilia but the disease did not occur in the recipient. The graft was successful and the recipient is alive till date.

Unrelated Umbilical Cord Blood Transplant for Children with ß-Thalassemia Major.

Beta thalassemia major, one of the most prevalent hemoglobinopathy throughout the word, can be cured by allogenic stem cell transplantation (SCT) (Bone Marrow Transplant 36:971-975, 2005). Many patients, however, lack a suitably matched related sibling donor. Unrelated umbilical cord blood (UCB) can be used as an alternative stem cell source for these patients. This report describes SCT for nine children with beta-thalassemia major using partially HLA-matched unrelated UCB. Conditioning included oral busulfan 16 mg/kg (day -10 to -7), cyclophosphamide (Cy) 200 mg/kg (day -5 to -2), fludarabine 90 mg/kg (day -13 to -11), and antithymocyte globulin (rabbit) 7.5 mg/kg (day -3 to -1). The infused cell dose was 10.71 × 10(7)/kg total nucleated cells (TNC) (range 6.5-17 × 10(7)/kg TNC). The patients ranged in age from 1.5 to 7 years, in weight from 10.5 to 17 kg. A second transplant with two unrelated cord blood units was attempted in two patients who had primary graft failure. The retransplant recipients were preconditioned with i.v Cy 120 mg/kg (day -3 to -2). Five of the nine patients engrafted promptly with 50-100 % donor chimerism (56 %). They engrafted at a median of 17 days (range 12-19). One patient is transfusion free for 36 months; a second patient is transfusion free for 18 months and a third is transfusion free for 9 months. There was no transplant related mortality. Four of the nine children had autologous recovery without engraftment. Primary graft rejection is the major complication. Post transplant complications were mild hepatic veno-occlusive disease, acute GVHD grade II, and CMV interstitial pneumonia. The chronic GVHD was limited and could be controlled by Methylprednisolone combined with Mycophenolate. The lack of a marrow donor registry in India makes UCBT from related and unrelated donors a good alternative. Transplant should be delayed until the child is at least 18 months of age. The dose of UCB stem cells is the most important factor for engraftment. UCB has the advantages of rapid availability and low risk of severe GVHD despite donor-recipient HLA disparity (Transplant Proc 37:2667-2669, 2005). We demonstrate the feasibility of this procedure in the setting of a developing country.

Neutropenic enterocolitis in a child with acute myeloid leukemia successfully treated with early surgical intervention.

Neutropenic entrocolitis (NE) is a life threatening complication of acute leukemia. The case presented here is of a 12 year old boy with acute myeloid leukemia, who developed neutropenic enterocolitis after induction with BFM-93 protocol. Patient underwent exploratory laparotomy during grade 4 neutropenia after failure on conservative line of management of NE. Patient withstood the procedure with supportive care and recovered. This case is reported because NE is a rare but potentially fatal complication and there are no clear guidelines for surgical intervention.