Journal of Pharmaceutical Research

Remya Antony ¹, Sandhya Lakshmi ¹, Akhila Sivadas ², Wesley M. Jose ³, Neeraj Sidharthan ⁴, K. Pavithran ⁵

Affiliations
1 Amrita School of pharmacy, IN
2 Department of Oncology, Amrita Institute of Medical Sciences (AIMS), Kochi, IN
3 Department of Medical Oncology & Hematology, Amrita Institute of Medical Sciences (AIMS), Kochi, IN
4 Department of Hematology, Amrita Institute of Medical Sciences (AIMS), Kochi, IN
5 Department, Medical Oncology & Hematology, Amrita Institute of Medical Sciences (AIMS), Kochi, IN

Abstract

Tumour Lysis Syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Hyperuricaemia is one of the prominent features of TLS which if not adequately prevented or treated can lead to renal failure requiring dialysis.

Rasburicase is the most recent agent indicated for treating TLS which is a recombinant urate oxidase enzyme that will oxidize uric acid to allantoin, a metabolite with 5-10 fold greater solubility than uric acid and reduces serum uric acid (SUA) levels within four hours of administration.

The recommended dose according to US Food and Drug Administration is 0.15 to 0.2 mg/kg/d for 5 days.

This retrospective study was aimed to evaluate the clinical efficacy of fixed low dose Rasburicase (1.5mg) in hyperuricemic patients who was admitted under Medical Oncology, Department in Amrita Institute of Medical Sciences And Research Centre, Kochi.

55 patient received Rasburicase during the study period of approximately 3years (July 2012 - June2015). 52 patients (94.54%) showed reduction in serum uric acid level in day 1 and by day 3.All patients (100%) had significant reduction in SUA after administration.

In this study we found that Rasburicase significantly lowered the serum uric acid level. Single dose of 1.5mg of rasburicase was found to be effective in rapidly correcting the hyperuricemia in all these patients. This can lead to considerable cost saving in the treatment and prevention of TLS occurring in patients with both solid tumors and hematological malignancies.

The advantage of Rasburicase over Allopurinol is its rapid onset of action, efficacy in patients with renal dysfunction and is well tolerated with very few side effects.

Keywords

Tumour Lyses Syndrome, Serum Uric Acid, Rasburicase.

Full Text

   

K. Sukanya Mathew ¹, C. Parvathy Priya ¹, Akhila Sivadas ², K. Pavithran ³

Affiliations
1 Amrita School of Pharmacy, Kochi, IN
2 Department of Medical Oncology, Amrita Institute of Medical Sciences, Kochi, IN
3 Department Medical Oncology, Amrita Institute of Medical Sciences, Kochi, IN

Abstract

Regorafenib is indicated for patients with metastatic colorectal cancer who have had previous treatment with multiple regimens. Here we report a 45 year old female who had carcinoma recto sigmoid and hemicolectomy with stage III disease.

She had adjuvant chemotherapy with 12 cycles of FOLFOX regimen [June 2011 - December 2011] and relapsed after 7 months. Then she was treated with Irinotecan 5FU/LV/Avastin for 6 cycles as a second line. She had a 6 months PFS from July 2012 - December 2012]. From January 2013 to October 2013, she was on follow up and the USG abdomen and PET scan showed relapse of the disease and so she was started on regorifinib 160 mg OD as the third line since November 2013.

After 2 weeks, she developed jaundice and hand foot syndrome and hence the dose was modified to 2 tablets/day. At this dose level she was tolerating it well and showed good clinical response. After 22 monthsrevaluation with CT scan, CEA showed progressive disease and hence chemotherapy was done again. She is in good performance status now with stage IV disease even after 50 Months from the diagnosis of stage IV cancer. Before the availability of these agents, the survival of these patients was less than 6 months. We emphasize that Regorifenib is an important role in the management of refractory metastatic colorectal cancer as a third line chemotherapy which has been approved by the US FDA.

Keywords

Regorafenib, Progression Free Survival (PFS).

Full Text

   

Sarada Kolathu ¹, Ranjini Pillai ², Akhila ², K. Pavithran ³

Affiliations
1 Amrita School of Pharmacy,Kochi, IN
2 Department of Oncology, Amrita Institute of Medical Sciences, Kochi, IN
3 Department Medical Oncology & Haematology, Amrita Institute of Medical Sciences, Kochi, IN

Abstract

Oxaliplatin is a new, third-generation platinum complex. It has a good safety profile characterized by low haematological-gastrointestinal toxicity.

It is commonly used in combination with 5-fluorouracil and folinic acid in the treatment of colorectal cancer. Neurotoxicity in the form of peripheral neuropathy is the most common side effect. However dysphonia and dysarthria are very rarely seen.

Here, we report a 54 year old female patient who presented with carcinoma colon. She underwent right hemicolectomy. CT scan abdomen showed stage 4 disease with multiple metastatic deposits in the liver. She was started on chemotherapy with CAPOX (Capecitabine/oxaliplatin). She tolerated well during the first cycle. After 2nd cycle, she developed diarrhoea and cellulitis and 3rd cycle was delayed. During the 3rd cycle, she complained of pain and spasm of jaw muscle and her voice was very feeble, which lasted for 1 hour even after the infusion was stopped. She was then prescribed half tablet of clonazepam 0.5mg and sedated; it took almost 15minutes more for relief followed by chemotherapy.

In a study conducted by Netherlands Pharmacovigilance Centre, 4 such cases of laryngospasm in association with the use of oxaliplatin reported. This can be managed by stopping the use of oxaliplatin and replacing with hydrocortisone, chlorpheniramine and lorazepam.

The acute reversible pattern of sensory neuropathy was observed in about 56% of study patients who received Oxaliplatin with 5-fluorouracil. Neurotoxicity is the dose-limiting side effect with this drug. This side effect can manifest as two distinct forms: the acute, reversible sensory neuropathy and a chronic, cumulative neuropathy.

The acute form occurs with infusion while the chronic toxicity does not become apparent until 8-10 cycles. The treatment of oxaliplatin-induced neurotoxicity needs to start at the bedside. Nursing staff and oncologists should inform patients to avoid drinking cold beverages. This can prevent pseudolaryngospasm. Promising strategies exist that include dosing modification, increasing infusion time and neuromodulatory agents which include Ca/Mg infusion, glutathione, carbamazepine, gabapentine, and amifostine.

Keywords

Oxaliplatin, Dysphonia and Dysarthria.

Full Text

   

Delcey Reachel Varghese ¹, Mary Sruthi Johny ², Akhila Sivadas ³, K. Pavithran ⁴

Affiliations
1 Amrita School of Pharmacy, Kochi, IN
2 Pharmacovigilance of India, AIMS, IN
3 Oncology Department, AIMS, IN
4 Department Medical Oncology & Hematology, AIMS, IN

Abstract

Adverse drugs reactions (ADRs) are noxious, unintended, and undesirable effects that occur as a result of drug treatment at doses normally used in man for diagnosis, prophylaxis, and treatment.

Due to the limitations of clinical trials, it is not possible to have a complete knowledge regarding all ADRs at the time of drug approval, necessitating drug safety follow-ups after releasing to the market. Pharmacovigilance has been defined as a science regarding the detection, assessment, understanding and prevention of ADRs, with its ultimate goal being improving pharmacotherapy. The most important finding of this study is the significant improvement in ADR reporting after education and establishment of Pharmacovigilance Centers.

In this study we collected and analyzed the adverse drug reactions reported by clinical pharmacist from oncology department to pharmacovigilance, 101 adverse drug reaction cases were reported from oncology to pharmacovigilance for a period of 11 months (September 2014-july 2015).

It was found that out of 101 cases, 51 males (50.49%) and 50 females (49, 50%) ADR cases were reported. Among which most reported were from between the age group 60-70 yrs (24 cases with 23.76%) with case of ALL (24 cases with 23.76%) which was treated with L-Asparginase.From the whole study done, itching (24 cases with 23.76%) was the most occurant Adverse Drug Reaction.

As a clinical pharmacist, it is our duty to encourage and educate other healthcare professionals for reporting adverse drug reactions.

We hereby conclude that clinical pharmacy service has an excellent role in designing and conducting the pharmacovigilance system in the hospitals by establishing specified centers with clearly defined objectives and tasks.

Keywords

PV (Pharmacovigilance), ADRs (Adverse Drug Reactions).

Full Text

   

Aloysius James ¹, Akhila Sivadas ², K. Pavithran ³

Affiliations
1 Amrita School of Pharmacy, Kochi, IN
2 Department of Oncology, Amrita Institute of Medical Sciences, Kochi, IN
3 Department Medical Oncology & Hematology, AIMS, Kochi, IN

Abstract

INTRODUCTION: Abiraterone acetate is a selective inhibitor of androgen biosynthesis that potently and irreversibly blocks CYP17, a crucial enzyme in testosterone and oestrogen synthesis, resulting in virtually undetectable serum and intratumoral androgens.

AIM: To study the clinical outcome of Abiraerone Acetate in castration resistant prostate cancer patients, by measuring their PSA (Prostate specific antigen) value.

To find out the effect of Abiraterone acetate on lab parameters(Serum Creatinine. Potassium, CBC) by administering this drug.

METHODS: This is a retrospective analysis to evaluate the efficacy and safety of abiraterone acetate in castration resistant prostate cancer patients. 14 men with CRPC who experienced treatment failure with one or more lines of treatment (hormonal manipulation or chemotherapy) were given abiraterone acetate (1,000 mg daily) with prednisone (5 mg twice daily).

RESULTS AND DISCUSSION: 42% patients shows good response in reduction in PSA value and 16% had progression and 42% had stable disease. Haemoglobin, Potassium and Serum Creatinine levels were not affected by Abiraterone. One patient had severe GI intolerance and the drug had to be stopped. In this study the final analysis shows that abiraterone acetate significantly lowered the PSA value and prolonged progression free survival in patients with metastatic castration-resistant prostate cancer who have progressed after first line or second line treatment. The median duration of drug exposure and overall average median survival of CRPC who received AA was found to be 11.1 months [range 3-18]. Abiraterone plus prednisone therapy can be given orally in an outpatient setting, providing an additional benefit for both patients and clinicians.

Keywords

Abiraterone Acetate (AA), Prostate-Specific Antigen (PSA), Castration-Resistant Prostate Cancers (CRPCS).

Full Text

   

Bini Vincent ¹, Akhila Sivadas ², Ameer Shahjahan ¹, K. Pavithran ³

Affiliations
1 Amrita School of Pharmacy, Kochi, IN
2 Department of Oncology, Amrita Institute of Medical Sciences, Kochi, IN
3 Medical Oncology & Hematology, Amrita Institute of Medical Sciences, Kochi, IN

Abstract

Oxaliplatin is a third-generation platinum analogue that is mainly used in the treatment of advanced colorectal cancer. The reported incidence of hypersensitivity reactions to oxaliplatin, especially after multiple cycles of therapy, is less than 1%.

Anaphylactic shock refers to anaphylaxis vasodilation , resulting in low blood pressure, severe bronchoconstriction.

Here we report a patient with adenocarcinoma of the colon who developed an anaphylactic shock following oxaliplatin administration during the sixth cycle of combination chemotherapy with FOLFOX-4 regimen (Oxaliplatin, 5-fluorouracil and leucovorin), despite the usual premedication with dexamethasone.

All the initial 10 cycles of chemotherapy with FOLFOX-4 was very well tolerated. He had a grade 1 neuropathy after his 9^th cycle and grade 2 in 10^th cycle. During his 11th cycle of chemotherapy, immediately after starting oxaliplatin, he developed severe hypotension, tachycardia, painful burning sensation all over the body and diffuse pruritis and was diagnosed to have anaphylactic shock. He responded to adrenalin, intravenous steroids and IV fluids and the reaction got resolved completely. After stabilization chemotherapy was continued by skipping oxaliplatin.

A Taiwan study in 2006 by Lee et al reported that 4 cases out of 303 patients who developed serious adverse reactions following oxaliplatin with an incidence of 1.32%.

Previous studies showed that anaphylaxis occurs after 7-9 cycles. Our patient developed during the 11^th cycle. Physicians should be vigilant on every patient on oxaliplatin especially after the first 6 cycles.

Since data are insufficient to proveprolongation of infusion time as well as the prophylactic use of steroid and antihistamines is effective, the rechallenge with oxaliplatin should be done only in selected patients.

Keywords

Oxaliplatin, Anaphylaxis.

Full Text

   

S. Sandhya Lekshmi ¹, Remya Antony ¹, Akhila Sivadas ², K. Pavithran ³

Affiliations
1 Amrita School of Pharmacy, Amrita Institute of Medical Sciences and Research Centre, Kochi, IN
2 Department of Oncology, Amrita Institute of Medical Sciences and Research Centre, Kochi, IN
3 Department Medical Oncology & Hematology, Amrita Institute of Medical Sciences and Research Centre, Kochi, IN

Abstract

Primary cutaneous large B-cell lymphoma, leg type (PCLBCL-LT), is a rare and aggressive neoplasm. Patients with PCLBCL, LT present with red to bluish nodules or tumors on one or both lower legs. Only about 10% to 15% of these patients are noted to develop lesions outside of the lower extremities. Compared with other subtypes of PCBCLs (PCMZL and PCFCL), these tumors are more aggressive with worse outcomes, as they frequently disseminate to lymph nodes and visceral organs.

Here we report a 56 year old male with multiple smooth swellings of varying size over the right shin with edema, which started as erythematous patches. He was treated with topical steroids and oral antibiotics. But lesion progressed so he was underwent skin biopsy. The biopsy reported as Primary cutaneous large B-cell lymphoma, leg type.

Initial PET-CT scan showed Non Hodgins lymphoma. He was staged to have stage IV. He was treated with Rituximab, cyclophosphomide, doxorubicin, vincristine, and prednisone (R-CHOP). After 4 cycles he attained complete response clinically and by PET-CT scan. After 6 cycles of R-CHOP, he was given local radiotherapy also. Post treatment he is on regular follow up and is doing well.

Keywords

PCLBCL-LT (Primary Cutaneous Large B-Cell Lymphoma, Leg Type), Non Hodgkins Lymphoma, R-CHOP.

Full Text

   

Karthika Ashok Kumar ¹, Akhila Sivadas ², A. S. Ananya Dutt ¹, Chanshi Chandran ¹, M. V. Thampi ³, K. Pavithran ⁴

Affiliations
1 Amrita School of Pharmacy, Kochi, IN
2 Department of Oncology, Amrita Institute of Medical Sciences, Kochi, IN
3 Department of Pathology, Amrita Institute of Medical Sciences, Kochi, IN
4 Department Medical Oncology & Hematology, Amrita Institute of Medical Sciences, Kochi, IN

Abstract

The discovery of 1p and 19q chromosomal arms deletion in glial tumors influences both more objective diagnosis and more accurate prediction of chemotherapy response.

As a result an attempt has been made to detect deletion using fluorescence in-situ hybridization (FISH) and analyzed its prognostic value in a cohort of glial tumor patients from Amrita Institute of Medical Sciences and Research Center Kochi.

FISH was performed on 66 FFPE tissue sections by using Vyis LSI 1p36/LSI 1q25 and LSI 19p13/LSI 19q13dual coloured FISH probe sets. Signals were scored from at least 150-250 non-overlapping, intact nuclei. 163 cases were analyzed. Both 1p and 19q deletions was observed only in 28/163 (17.17%), - 1p/+ 19q deletion 80/163 (49.07%) and+1p/-19q deletion 55/163(33.74%) .

In this work presented the FISH was successfully applied to identify deletion 1p/19q. Its incidence depends on the type of diagnosed gliomas. In contrast to reported data, the present study reveals 49.07% deletion - 1p/ + 19q.

Deletions also have prognostic significance in the test group what constitutes the basis for inclusion of determining deletion 1 p/19q into diagnostic and treatment algorithm.

Keywords

FISH, Deletion 1p/19q, Glioma.

Full Text

   

Jisha S. Das ¹, Akhila Sivadas ², Ameer Shajahan ¹, K. Pavithran ³

Affiliations
1 Amrita School of Pharmacy, Kochi, IN
2 Department of Oncology, Amrita Institute of Medical Sciences, Kochi, IN
3 Department Medical Oncology & Hematology, Amrita Institute of Medical Sciences, Kochi, IN

Abstract

Cardiotoxicity associated with 5-fluorouracil (FU) is an uncommon, but potentially lethal, complication. Cardiac toxicity of 5FU include acute coronary syndrome (ACS), cardiomyopathy, vasospastic angina, coronary thrombosis and dissection, malignant arrhythmias, and sudden cardiac death.

With shorter bolus regimens, the incidence of cardiotoxicity typically lies between 1.6% to 3% of cases and with more prolonged regimens, these percentages increase to 7.6% to 18%.

We intend to share four cases which showed cardiac toxicity on chemotherapy with 5FU.

All our patients were getting continuous infusion regimens. 2 patients had arrhythmias one SVT and one bradycardia), one had reversible cardiomyopathy and one had acute coronary vasospam.

2 patients were suffering from carcinoma esophagus and one from carcinoma nasopharynx and another from cholangiocarcinoma. All were not having any cardiac risk factors. In all our cases the event was completely reversible. Except in the patient who had cardiomyopathy, chemotherapy was continued without any further issues.

Here we Concluded With increased usage of 5-FU for the treatment of gastrointestinal malignancies, cardiotoxicities may be expected to be encountered more frequently in the future. A pre-chemotherapy history, physical examination and a basic cardiac evaluation and monitoring in high risk cases might be able to prevent such events.

Keywords

5-FU, Cardiotoxicity.

Full Text