Lenalidomide History

Lenalidomide, which is sold under the name of revlimid, is used for the treatment of MM (Multiple Myeloma) and myelodysplastic syndromes (is a group of cancers in which immature blood cells in the bone marrow do not mature, so do not become healthy blood cells).

Before knowing history, one needs to know that thalidomide, a pioneer to lenalidomide, was not developed for the treatment of multiple myeloma. It is said that the history of lenalidomide is one of the most interesting stories in medical science. In the late 50s when thalidomide developed it was known as sleeping pills because people feel sleepy after taking that. And when it was developed no one knew about the exact mechanism of medication.

In the early 60s when pregnant women inhaled thalidomide for morning sickness it was observed that they gave birth to babies with malformations. After that, it was felt that the drug is for some other mechanism too.

In 1971, the concept discovered called anti-angiogenesis which involves blocking the formation of new blood vessels important for a tumor to survive. Then only this showed progress by preventing the growth of new blood vessels. Then when thalidomide and then lenalidomide came into the spotlight.

Approval history

On December 27, 2005, lenalidomide was first approved by the US Food and Drug Administration for the treatment of multiple myeloma who received at least one prior therapy.

Dosage and usage 

After knowing about the history of lenalidomide, it is important to know about the drugs how and when to consume them. First of all, it is recommended to consult the doctor, and is not advisable to consume any drug dose without the doctor's prescription.

The lenalidomide is in a form of a capsule and strength of 2.5mg, 5mg, 10mg, 15mg, 20mg, and 25mg. Lenalidomide is suggested to be taken daily once orally at the same time. Lenalidomide should be swallowed fully with water and not break, crush or split.

Usage of medication in Multiple Myeloma (MM) as starting dose is 25mg once daily from Day 1 to day 21 repeated 28 days cycle.

Later we all see this part called pricing. Lenalidomide price in India is different and depends on different trade such as 

• Lenalid cost approximately Rs. 4386 – Rs. 9297
• Lenmid cost approximately Rs795 –Rs 2797
• Lenid cost approximately Rs 1500 – Rs 2900

Carfilzomib along with immunomodulatory drugs, and dexamethasone for Relapsed/Refractory Multiple Myeloma

The triplet carfilzomib, immunomodulatory drugs, and dexamethasone has shown effective outcomes for the treatment of relapsed/refractory (R/R) multiple myeloma.

Apart from this, for numerous authorities, this combination has a little bit of a high cost. On behalf of new data, this triplet (carfilzomib, thalidomide, and dexamethasone) could be a safe as well as a cost-effective alternative.

The carried out study enrolled patients with relapsed/refractory MM who had between 1 to 3 prior lines of treatment. Total 83 of the patients had a median age of about 66 years. Patients were taken 12 cycles, each lasting one month, of this triplet.

The main result that is measured at the end of a study in order to see if a given treatment worked was PFS (Progression-Free Survival). Secondary endpoints were ORR (Overall Response Rate), OS (Overall Survival), SE (side effects), and QoL (Quality of Life).

The median progression-free survival was noted as 20 months. The progression free survival rate at 6.5 months was noted as 76.2%. Median OS has not been achieved in the carried out study. The combination achieved an overall response rate of 86.4%.

Maximum side effects noted in the study population were grade 2 or lower. The most commonly reported side effects were peripheral neuropathy, with 16% of patients reporting, followed by upper respiratory tract infections in 12% of patients. Those most recent data indicates that 41% of patients have completed 18 cycles of treatment.

An interview was held in between Targeted Oncology and Hang Quach, MD, a consultant clinical and laboratory haematologist at St. Vincent’s Hospital, in which Hang Quach discussed the phase-II Australasian Leukaemia and Lymphoma Group multiple myeloma 018/ Asian Myeloma Network 002 study and how it can be responsible for impacting the treatment of relapsed/refractory MM in the future.

Reference:

https://www.targetedonc.com/view/expert-reviews-results-of-carfilzomib-combination-in-r-r-multiple-myeloma

Zoledronic Acid: A Bisphosphonate Therapy

Zoledronic acid injection, also addressed as zoledronate, specifically is a drug prescribed for the treatment of bone diseases including high blood calcium due to cancer, bone breakdown due to cancer, osteoporosis, and Paget’s disease of bone. 

Mechanism of Action: Zoledronic acid falls under a class of substances named Bisphosphonates. It binds specifically to bone and it does not stay in your blood. The zoledronic acid injection helps in order to slow down the bone resorption (caused by osteoclasts) which enables the bone-forming cells (osteoblasts) time in order to rebuild the normal bone.

Dosage & Administration: The zoledronic acid injection is administered as an infusion into a vein for 15 minutes by your healthcare practitioner. 

Your healthcare practitioner will recommend you to consume at least 2 glasses of water (500 mL or 2 cups) prior to and following the treatment.

In order to prevent Osteoporosis, 5 mg should be given as a single dose.

In order to prevent Paget’s disease, 5 mg should be given as a single dose.

The zoledronic injection may work for over 1 year, and your healthcare professionals will inform you in case you need to be treated again. 

It is crucial to take calcium as well as vitamin D supplements as directed by your healthcare practitioner in order to reduce the probability of having reduced blood calcium levels, to prevent the loss of bone and to help rebuild the bone.

Possible Side Effects: Like all drugs, zoledronic acid injection may also be responsible for causing some unwanted adverse reactions in addition to its beneficial effects.

The most common zoledronic acid side effects include:

• Fever
• Fatigue
• Chills
• Headache
• Nausea
• Vomiting
• Abdominal pain
• Diarrhea
• Back pain
• Pain in extremity
• Influenza-like illness
• Weakness
• Pain
• Shortness of breath
• Dizziness
• Excessive sweating
• Tiredness
• Disturbed digestion
• Decreased appetite
• Non-cardiac chest pain
• Malaise (unwell feeling)
• Bone, joint or muscle pain or stiffness

Other side effects: There's possibility that some other side effects due to zoledronic acid infusion may also occur, which are listed as follows:

• Numbness
• Tingling sensations
• Allergic reactions
• Urinary tract infection
• Constipation
• High blood cholesterol levels
• Pain in jaw
• Pain in neck
• Joint sprain
• Post-traumatic pain
• Cough
• Seasonal allergy
• Vaginal dryness
• Congestion of the nose
• Pharyngolaryngeal pain 
• Increased or irregular heartbeat
• Rheumatoid arthritis/arthritis (inflammation of the joints)

Warning & Precautions:

• Administration of zoledronic acid injection is not recommended for patients aged under 18 years.
• Prior to taking zoledronate infusion talk to your doctor if you're unable to take daily calcium/vitamin D supplements. 
• Ensure that you have talked about zoledronic acid injection treatment with your healthcare practitioner. 
• In case you're taking treatment with another intravenous form of zoledronic acid 4mg, you're not allowed to be treated with the zoledronic acid injection.
• In case you're being treated with this injection, treatment should be avoided with other bisphosphonates (such as risedronate, alendronate, clodronate, etidronate, pamidronate and ibandronate) at the same time.
• Use of zoledronate is not recommended in case you are pregnant or plan to become pregnant or are breast-feeding.
• Talk to your healthcare practitioner in case you've any pain in your hip, groin, or thigh. This injection may be responsible for causing the unusual fractures in the thigh bone.
• Inform your doctor if you've a sudden headache, numbness in your limbs, confusion, trouble talking, vision problems, and trouble walking.
• Tell your healthcare team if you have kidney problems. Cases of worsening of kidney function, including kidney failure may happen when you take the zoledronic acid 4mg injection.

Drug Interactions: You need to inform your healthcare team in case you're taking or have recently taken any other drugs, including any kind of drug you have bought without a prescription. It is specifically crucial for your healthcare team to know if you are taking :

• any drugs known to be harmful to your kidneys (such as Non-Steroidal Anti-inflammatory Drugs).
• water pill (diuretics)
• aminoglycoside antibiotics (a type of drug used to treat severe infections).

Drug Overdose: In case you have received or taken too much zoledronic acid dose, contact your healthcare practitioner, hospital emergency department as soon as you can, even if there are no signs and symptoms.

Storage Guidelines: Store these injections at the room-temperature between 15°C-30°C. Original packaging should be kept unchanged as well as sealed until a healthcare practitioner administers the inj zoledronic acid. Don't forget to keep the injection and all drugs safely away from the children.

Cost: The zoledronic acid price may vary from branded (innovator) to non-branded (generic) drugs. The price for a bottle of Aclasta 5mg/100ml Infusion (Trade Name) is around 20492 INR. 

Frequently Asked Questions:

From which class of drug Zoledronic acid belongs? 

Zoledronic acid specifically belongs to a class of drugs named bisphosphonates that helps in order to prevent the abnormal breakdown of bones.

What is Zoledronic acid? What is it used for?

Zoledronic acid is used in order to prevent and treat osteoporosis and fractures in patients with metastatic cancer (a cancer which spreads to newer areas of the body). This drug can also be used in order to treat hypercalcemia (elevated blood calcium levels).

How should Zoledronic acid be given? 

Zoledronic acid is given by injection into a vein.

How does Zoledronic acid act? 

Zoledronic acid acs in order to block the activity of osteoclast cells and thus reduces the bone breakdown. 

How long should I take Zoledronic acid?

This medication should be taken in the dose as well as duration recommended by healthcare professionals. Zoledronic takes around 6-month in order to show its maximum benefits on bones. Although, in certain cases, the healthcare practitioner may suggest this medication for a longer period of time. The appropriate duration will depend on the condition you're currently being treated for.

What are the commonly reported side effects of Zoledronic acid? 

Commonly reported side effects of Zoledronic acid include joint pain, high blood pressure, fever, diarrhea, and feeling tired.

What are the severe side effects of Zoledronic acid? 

Severe side effects of Zoledronic acid may include low blood calcium, osteonecrosis of the jaw and kidney problems. 

What if Zoledronic acid is used during pregnancy? 

Use of zoledronic acid during pregnancy may be responsible for harm to the baby.

NOTE: The information provided about zoledronic acid injection in this article is only for informational purposes and is not served as a substitute for the medical treatment, consultation, diagnosis, of a qualified healthcare practitioner.

Squamous Cell Carcinoma- A type of skin disease

 What is Squamous cell carcinoma of the skin?

Squamous cell carcinoma (SCC) specifically is a kind of skin cancer that originates from the squamous cells of the skin. These cells are quite different from melanocytes (from which melanomas originate) as they do not usually play a role in the color of skin but compose the maximum skin’s most superficial layer, the epidermis.

How does Squamous cell carcinoma look like?

It usually looks like wounds or elevated growths that may bleed without scratching and do not heal over time. Squamous cell carcinoma may also look like scaly patches or parts of skin covered by a thick crust, surrounded by a deep red area that looks inflamed. Some squamous cell carcinoma may also resemble warts. They usually occur in sun exposed parts such as the scalp, face, rim of the ears and the back of the hands, but may also be developed on the lips as well as the genital organs.

How common is Squamous cell carcinoma? 

On behalf of existing data, SCC is known as the second most common skin cancer in the Caucasian populations and the most common skin cancer in persons of color. 

Squamous Cell Carcinoma Causes: This disease is caused basically by cumulative exposure to the sun (ultraviolet-UV) throughout a person’s life. This may include daily year-round exposure to the sun and the more intense exposure experienced while on the months of summer. Additionally, UV exposure due to tanning bed use may also be responsible for causing the damage of skin that can lead to the formation of Squamous Cell Carcinoma.

Squamous Cell Carcinoma Risk Factors: People who are with fair skin, light hair, freckles and blue, green, or gray eyes are at comparatively higher risk of developing SCC. In addition, those patients who are with diseases such as psoriasis that have undergone phototherapy treatments, or transplant patients that take immunosuppressive medications are also at risk. Regardless of any individual’s personal medical history, extensive sun exposure is also quite associated with a higher risk of occurring this kind of skin cancer.

Using tanning beds is also responsible in order to increase the risk of Squamous Cell Carcinoma substantially. Specifically, it is believed that patients using tanning beds have a multiple times higher risk of developing Squamous Cell Carcinoma than those that do not. Patients of color may also develop Squamous Cell Carcinomas on parts of preexisting inflammatory skin conditions, burn injuries or serious trauma.

Squamous Cell Carcinoma Symptoms: Patients that have new or growing lesions on the skin, or ulcers that fail to heal should contact their dermatologist for a consultation. Patients with a history of extensive exposure to sun, phototherapy or tanning beds may occur one or multiple small red scaly patches on their skin. Sometimes such patches can be skin-colored but may feel rugged at the time of touch. 

These lesions are named actinic keratoses and usually are considered as premalignant lesions that may be responsible for causing squamous cell carcinoma. If a patient observes such a lesion they must refer to a dermatologist in order to get appropriate treatment.

Squamous Cell Carcinoma Diagnosis and Treatment: It is basically diagnosed by performing a skin biopsy. The choice of treatment for Squamous Cell Carcinoma is surgical excision. This sort of surgery usually needs the use of topical anaesthesia only. Then, the skin is closed with stitches or a skin graft. Another sort of treatment can be considered for squamous cell carcinoma is radiotherapy. This kind of treatment may need multiple sessions in order to leave an effective effect. In a few cases, a combination of surgery and radiotherapy can be used, while in a few, quite advanced tumors, chemotherapy can also be recommended. 

Squamous Cell Carcinoma Prognosis: Most squamous cell carcinomas have an amazing prognosis, as if they are diagnosed a bit early, can be treated successfully with the help of surgical excision only. Although, about 2 to 5% of Squamous Cell Carcinomas have been reported to give metastases. Overall, the five-year relative survival rate has been reported for patients with squamous cell carcinoma.

What can individuals do in order to avoid getting an SCC (Squamous cell carcinoma)?

The use of various sun protection methods is quite necessary in order to prevent squamous cell carcinoma. These can include the rigorous use of UVA and UVB, seeking shade on the beach and wearing sun protective clothing, hats as well as sunglasses. The use of tanning beds needs also to be avoided.

NOTE: The information provided in this article is only for informational purposes and is not served as a substitute for the medical treatment, consultation, diagnosis, of a qualified healthcare practitioner.

Related:- What is Basal Cell Carcinoma

Temozolomide: An Oral Alkylating Agent

What is temozolomide: 

As an oral alkylating agent, Temozolomide is approved in order to treat newly diagnosed glioblastoma multiforme and refractory anaplastic astrocytoma. 

How is temozolomide dosed: The daily dose of temozolomide capsules for a given patient is usually calculated by the healthcare practitioner, based on the patient's body surface area (BSA). The resulting dose is then rounded off to around 5 mg.

The temozolomide dose for subsequent cycles can be adjusted according to nadir neutrophil as well as platelet counts in the previous cycle and during the time of starting the next cycle.

Treatment regimen: Temozolomide is recommended to be given for 5 consecutive days on a 28 day cycle. Patients need to continue taking temozolomide 20 mg until their healthcare practitioner determines that their disease has progressed, up to 22 months, or unt
il unacceptable adverse reactions or toxicities occur. 

How is temozolomide taken:

Patients should consume a daily dose with a full glass of water at about the same time every day. Taking the capsules on an empty stomach or at bedtime may help in order to ease the nausea. In case patients are also taking antinausea or other drugs to relieve the adverse reactions associated with temozolomide 5 mg, they are advised to take these drugs 30 minutes prior to taking temozolomide.

Apart from this, you may receive this drug by injection into a vein (intravenous). Your healthcare provider will decide the appropriate way for you to take this medicine. 

How is temozolomide capsules supplied: 

The drug temozolomide comes as capsules in 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, and temozolomide 100 mg strengths. The temozolomide capsules basically contain a white capsule body with the white cap.

Possible Side Effects: Common temozolomide side effects include:

• Nausea
• Vomiting
• Headache
• Feeling tired
• Hair loss 
• Constipation
• Bruising
• Rash
• Diarrhea
• Weakness
• Fever
• Dizziness
• Memory loss
• Loss of appetite
• Viral infection
• Sleep problems
• Coordination problems
• Infusion site reactions
• Paralysis on one side of the body

Tell your healthcare practitioner about any possible side effect that bothers you or that does not go away.

Who should not take this drug: Do not take Temodar in case you:

• have had an allergic reaction to DTIC (dacarbazine), another cancer drug.
• have had a red itchy rash, or a severe allergic reaction, such as trouble breathing, swelling of the face, throat, or tongue, or severe skin reaction to temozolomide injection or any of its ingredients. If you are not sure, ask your doctor. 

Precautions: Inform your healthcare practitioner about all your medical conditions, including:

• in case you are allergic to dacarbazine (DTIC) or have had a severe allergic reaction to temozolomide injection.
• in case you have kidney problems. 
• in case you have liver problems. 
• in case you are pregnant.
• in case you are breast-feeding. This drug may pass into breast milk. You and your doctor should take a decision if you will breast-feed or take temozolomide 100 mg. You must avoid doing both without interacting with your healthcare team.

Storage Guidelines: Store the capsules at 77°F (controlled room temperature). Storage at 15°C to 30°C is permitted occasionally. The temozolomide capsules should be placed out of the reach of children and pets.

How much does temozolomide cost? 

The temozolomide cost may vary from generic to innovator drugs. Prices may range from around 2050 INR to around 25000 INR. 

NOTE: The information provided in this article is only for informational purposes and is not served as a substitute for the medical treatment, consultation, diagnosis, of a qualified healthcare practitioner.

All you need to know about Pegaspargase

What is Pegaspargase?

Pegaspargase (Oncaspar) is used for the treatment of patients with acute lymphoblastic leukemia (ALL).

The pegaspargase is a composition of Oncaspar, which is an enzyme that breaks down asparagine, an essential building block of proteins without which it is difficult to survive for cells. Healthy cells often produce asparagine for themselves, while cancer cells cannot. This medication decreases the level of asparagine in the blood cancer cells and resists the cancerous cells in order to grow.

How does pegaspargase work?

Pegaspargase is specifically involved in breaking down the amino acid asparagine to aspartic acid as well as ammonia. 

The leukemic cells are not able to produce their asparagine and depend on circulating the asparagine for the growth; apart from this, the asparaginase deprives the leukemic cells in order to circulate the asparagine responsible for death of the leukemic cell.

How Oncaspar is given?

Pegaspargase Injection should be administered as an intravenous (IV) infusion over 1-2 hours or maybe given as an intramuscular injection (IM).

Possible side effects: Like all medications, oncaspar can cause side effects, although not everybody gets them.

Very common side effects are as follows:

• Weight loss
• Leg pain
• Chest pain
• Shortness of breath
• Loss of appetite
• General weakness
• Vomiting
• Diarrhoea
• Nausea
• Increased blood sugar levels
• Changes in the function of the pancreas

Common adverse reactions may include:

• Ascites
• Fever and flu-like symptoms
• Mouth sores
• Back, joint or abdominal pain
• High levels of fat
• Increased cholesterol
• Low potassium in blood
• Decreased number of red blood cells

There are some rare pegaspargase side effects, which may include:

• Headache
• Confusion
• Seizures and visual loss 
• Reversible posterior leukoencephalopathy syndrome (RPLS)

warnings and precautions:

Discuss with your doctor prior to receiving pegaspargase. It may inappropriate or not suitable for individuals:

1. If individuals have had serious allergic reactions, for instance itching, flushing or swelling of the airways, because major allergic reactions to this drug may occur.
2. If individuals suffer from a bleeding disorder or have serious blood clots.
3. If individuals get a fever. It may make you comparatively more susceptible to the infections.
4. If individuals have had poor liver function or are taking other medicines which may be harmful for liver. When this drug  is used along with other cancer treatments, liver and central nervous system damage may occur.
5. If individuals suffer from abdominal pain. Inflammation of the pancreas, that in some cases causes death, may develop with pegaspargase injection treatment.
6. This medicine may lead to fluctuations in clotting factors and can increase the risk of bleeding/clotting.
7. If individuals are the parents of a child and are taking treatment with this drug, talk to your doctor if any of the above terms apply to your child.
8. If individuals are pregnant or breast-feeding, or are planning to have a baby, ask your healthcare team for advice prior to using this medication. 

Who should not use Pegaspargase? 

1. Patients who are allergic to pegaspargase or to any of the other ingredients of this medicine.
2. Patients who have severe hepatic disease.
3. Patients who have ever had pancreatitis.
4. Patients who have ever had severe bleeding following asparaginase therapy.
5. Patients who have ever had blood clots following asparaginase therapy.

Inform your doctor in case any of such terms apply to you. In case you are a parent of a child who is taking treatment with pegaspargase, please discuss with your doctor if any of them apply to your child.

If you are given too much Oncaspar: As a healthcare practitioner will administer the oncaspar, it is quite unlikely patients will be given wrong dosage. 

In the event of an accidental drug overdose, patients will be monitored by the healthcare team and treated accordingly.

In case you want to know something on the use of this drug, ask your doctor.

How to store Oncaspar? 

Keep the oncaspar 3750 out of the sight and reach of children. Should be stored in the refrigerator (2°C-8°C).

Freezing of medication is not recommended. Following the medicinal product has been reconstituted and diluted, the solution must be used as soon as possible. If the diluted solution can not be used immediately, it should be stored at 2°C-8°C for up to 48 hours.

NOTE: The information provided in this article is only for informational purposes and is not served as a substitute for the medical treatment, consultation, diagnosis, of a qualified healthcare practitioner.

Addition of Pemetrexed and Carboplatin to Gefitinib Doubled PFS in Patients with EGFR-Mutant NSCLC

On behalf of derived outcomes of a randomized phase 3 study came into view in the Journal of Clinical Oncology, adding pemetrexed and carboplatin to gefitinib significantly enhanced the progression free survival and OS for participants with NSCLC and EGFR-sensitizing mutations. 

Although data suggests that the clinically relevant severe toxicities have been observed twice as often with the combination regimen than with gefitinib alone.

According to Vanita Noronha, MD, MBBS, professor in the department of medical oncology at Tata Memorial Hospital in Mumbai, India, and colleagues, “Apart from the detection of molecular target and using medications, believed to bind to the target, cure and long-term remission elude us,” “Resistance inevitably occurs within 8-12 months. Number of ways have been implemented in order to reduce the emergence of resistance. One strategy involved in order to combine the cytotoxic chemotherapy with an EGFR TKI.” She added. 

Between August 2016 and August 2018, in an open-label study conducted by Noronha and colleagues, total 350 participants enrolled with advanced, chemotherapy-naive, EGFR-mutated Non-Small Cell Lung Cancer. About 18% of participants had brain metastases and 21% found with an ECOG performance status of 2.

The investigators differentiated patients on the basis of performance status and EGFR mutation type and randomly assigned them 1:1 to gefitinib 250 mg orally once per day alone (n = 176; median age, 56 years; range, 27-78) or with pemetrexed 500 mg/m2 IV and carboplatin IV area under the curve 5 each 3 weeks for the four cycles (n =174; median age, 54 years; range, 27-75). The combination regimen was followed by maintenance pemetrexed 500 mg/m2 IV every three weeks.

The progression free survival represents as the primary endpoint, and OS, toxicity and RR represent as the secondary endpoints. The researchers specified survival endpoints in the intention in order to treat the population. The median follow-up reported about 17 months.

About 80% of participants treated with gefitinib and chemotherapy, completed all four cycles of pemetrexed and carboplatin. Outcomes represented ORR of about 75.3% among participants in the combination population and 62.5% in the gefitinib-only population. Participants in the combination population had longer median progression free survival than those in the gefitinib-only population. The combination population had significantly longer median overall survival than the gefitinib population.

About 50% of patients in the combination population experienced grade 3 or higher toxicities; maximum because of the chemo induced myelosuppression and nephrotoxicity, compared with 25.3% of those in the gefitinib population.

Researchers have written, “Adding pemetrexed and carboplatin to gefitinib prolonged PFS (progression free survival) and overall survival, but also be responsible for increasing the toxicity."

Also, Jennifer Byrne stated that, "The pemetrexed, carboplatin and gefitinib, together appeared as a new standard first-line therapy for patients with the EGFR-mutant Non-Small Cell Lung Cancer.”