Day 14 A Month of Teal: Chemotherapy on Initial Diagnosis

The section below is an excellent description of the chemotherapy drugs used for ovarian cancer. It can be found in full on the  Cancer.net website sponsored by ASCO.

Ovarian, Fallopian Tube, and Peritoneal Cancer: Treatment Options

http://www.cancer.net/cancer-types/ovarian-fallopian-tube-and-peritoneal-cancer/treatment-options

"Chemotherapy is the use of drugs to destroy cancer cells, usually by stopping the cancer cells’ 
ability to grow and divide. Chemotherapy is given by a gynecological oncologist or a medical oncologist, a doctor who specializes in treating cancer with medication.
Systemic chemotherapy gets into the bloodstream to reach cancer cells throughout the body. Common ways to give chemotherapy include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed (orally).
A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a set period of time. A patient may receive one drug at a time or combinations of different drugs at the same time.
Most of the chemotherapy options described below apply to epithelial ovarian cancer, as well as fallopian tube cancer and peritoneal cancer. The type of the chemotherapy used depends on several factors.

• Adjuvant chemotherapy. This is done to destroy cancer remaining after surgery. This treatment typically consists of carboplatin (Paraplatin) given with paclitaxel (Taxol) or docetaxel (Docefrez, Taxotere) intravenously (IV), which is through the vein. Most of these drugs are given every 3 weeks. 
  Another approach is called “dose-dense” chemotherapy. This is when the drugs are giving weekly instead of every 3 weeks. Some studies show that using dose-dense paclitaxel with carboplatin may improve survival rates compared to giving the drugs every 3 weeks. Talk with your doctor about which scheduling option is best for your situation. (The  recent ICON 8 study reported on at #ESMO17 found no difference in survival between dose dense and every 3 week chemotherapy http://www.esmo.org/Conferences/ESMO-2017-Congress/Press-Media/Press-Releases/ICON8-Trial-Reaffirms-Standard-Dosing-in-Ovarian-Cancer-Chemo)
  
  
  In addition, a third way to give adjuvant chemotherapy is to infuse it directly into the abdomen. This is called intraperitoneal or “IP” chemotherapy. This approach can be considered for women with stage III disease after a successful surgical debulking procedure. In previous studies, IP treatment was more effective when compared to intravenous treatment on the every 3-week schedule.
  
  Studies comparing dose-dense (weekly) IV chemotherapy with carboplatin and paclitaxel to IP chemotherapy with the same drugs show similar outcomes. Doctors are discussing whether the more intense IV approach can replace the use of IP chemotherapy.
  
  With each of these approaches, doctors consider a variety of factors, such as age, kidney function, and other existing health problems.
  
  Research studies are underway to see if additional medications, such as PARP inhibitors, should be used. Several studies have evaluated whether adding bevacizumab (Avastin), which is an anti-vascular or “blood vessel growth blocking” antibody, to standard chemotherapy following initial surgery is helpful. In general, bevacizumab used for ovarian cancer has prolonged the time in some patients before the cancer returns; see Latest Research."
  
  
  Additional information on chemotherapy may be found on these pages:
  https://www.nccn.org/patients/guidelines/ovarian/index.html 
  http://www.foundationforwomenscancer.org/types-of-gynecologic-cancers/ovarian/chemotherapy/
  
  
  Dee
  Every Day is a Blessing!
  
  

Ovarian Cancer Treatment: Chemotherapy

For the majority of  women diagnosed with ovarian cancer chemotherapy will follow surgery.

What is Chemotherapy?
Chemotherapy is the use of chemical drugs to kill the fast growing cancer cells.

For ovarian cancer the standard drugs used on initial diagnosis depends on stage at diagnosis. Below are the recommended chemotherapy treatments as given in the NCCN guidelines.

Stage I
Carboplatin with paclitaxel or docetaxel - IV ( intravenous)

Stage II, III, IV
Paclitaxel with cisplatin IP ( intraperitoneal injection)
Paclitaxel or docetaxel with Carboplatin - IV
Dose Dense  Paclitaxel with Carboplatin  - IV

The chemotherapy is given in cycles every 14, 21 or 28 days. I wrote about how different chemotherapy drugs work in this blog post. (http://womenofteal.blogspot.com/2012/01/how-do-those-ovarian-cancer-treatments.html)

IP, intraperitoneal chemotherapy allows the drugs to be injected into the peritoneal cavity . Studies have shown that treatment with IP / IV increase increases survival by 16 months over IV treatment alone.

Chemotherapy Drugs for Recurrences: 

When a women's cancer recurs she may be offered the same chemotherapy drugs or one of these approved drugs as found on the NCI website.

• Carboplatin
• Clafen (Cyclophosphamide)
• Cisplatin
• Cyclophosphamide
• Cytoxan (Cyclophosphamide)
• Doxorubicin Hydrochloride
• Dox-SL (Doxorubicin Hydrochloride Liposome)
• DOXIL (Doxorubicin Hydrochloride Liposome)
• Doxorubicin Hydrochloride Liposome
• Evacet (Doxorubicin Hydrochloride Liposome)
• Gemcitabine Hydrochloride
• Gemzar (Gemcitabine Hydrochloride)
• Hycamtin (Topotecan Hydrochloride)
• LipoDox (Doxorubicin Hydrochloride Liposome)
• Neosar (Cyclophosphamide)
• Paclitaxel
• Paraplat (Carboplatin)
• Paraplatin (Carboplatin)
• Platinol (Cisplatin)
• Platinol-AQ (Cisplatin)
• Taxol (Paclitaxel)
• Thiotepa
• Topotecan Hydrochloride

 Tomorrow's post will be on targeted therapies for ovarian cancer.
 
Dee
Every Day is a Blessing! 


Source:
NCCN guidelines
http://www.nccn.org/patients/guidelines/ovarian/index.html#42
JCO:
http://jco.ascopubs.org/content/early/2015/08/03/JCO.2015.61.4776.abstract

How Do Those Ovarian Cancer Treatments Work?

I have always been interested in how cancer treatments work to destroy cancer cells. The other day I was talking to another ovarian cancer survivor on the phone. She was deciding between two treatments for a recurrence. When I hung up the phone I realized that I knew the side effects of the treatments but I really didn't know how they worked to kill off the cancer cells. So I decided to do some research on the NCI site to find the answer.

Here is a summary of the popular Chemotherapy treatments, drugs and biologics, used in the treatment of Ovarian Cancer. More complete information can be found at http://www.cancer.gov/drugdictionary

Paclitaxel ( Taxol) & Abraxane

“binds to and stabilizes microtubules,preventing their depolymerization and so inhibiting cellular motility, mitosis and replication”

Remember high school biology and the steps of cell reproduction. This drug affects that process. Abraxane is similar to Paclitaxel but does not use a solvent which causes side effects so it permits the administration of larger doses.

Carboplatin

“binds to GC-rich sites in DNA , thereby inducing intrastrand and interstrand DNA cross-link, as well as DNA-protein cross- links...results in apoptosis and cell growth inhibition.”

This platinum drug binds to the Guanine and Cytosine rungs on the DNA helix and causes cell growth to stop and then cell death occurs.

Gemcitabine ( Gemzar)

“is converted intracellularly to the active metabolites dFdCPD and dFdCTP... thereby decreasing the deoxynucleotide pool available for DNA synthesis and ... is incorporated into DNA , resulting in DNA strand termination and apoptosis.”

Inside the cell the drug is incorporated in its modified form into the DNA strands and leads to cell death.

Topotecan

“topotecan selectively stabilizes topoisomerase I-DNA covalent complexes, inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when complexes are encountered by the DNA replication machinery.”

Breaks in the strands of DNA caused by the topotecan prevents the DNA from replicating correctly and cell reproduction is inhibited.

Etoposide

“etoposide binds to and inhibits topoisomerase II and its function in ligating cleaved DNA molecules, resulting in the accumulation of single- or double-strand DNA breaks, the inhibition of DNA replication and transcription, and apoptotic cell death.”

Etoposide causes breaks in the DNA thereby affecting cell reproduction and leads to cell death.

Bevacizumab ( Avastin)

“Bevacizumab binds to VEGF and inhibits VEGF receptor binding, thereby preventing the growth and maintenance of tumor blood vessels.”

Cancer cells create blood vessels. Bevacizumab is a monoclonal antibody that binds to the vascular endothelial growth factor which helps create and maintain those cancer cell's blood vessels.

Dee

Every Day is a Blessing!

Chemo Drug Shortages

Over the past few weeks I've been reading a number of articles on chemotherapy drug shortages. Here is just one video and article on the topic.

On June 16, 2011 Paclitaxel the generic brand of Taxol was put on the American Society of Health System Pharmacists current shortage list(ASHP). These drugs are manufactured in various milligram dosages from 6mg too 300 mg. The reasons given in the bulletin were:

Manufacturing shortage - Teva

Increased demand - APP

No reason - Bedford

There is no direct substitution for paclitaxel.

On June 23,2011 ASHP added carboplatin solution for injection to the list.

The reason for the shortage was given as:

Manufacturing shortage- Sandoz, Teva, Hospira

Discontinued manufacturing in May 2011- Bedford

These two chemotherapy drugs are the standard of care for women initially diagnosed with ovarian cancer and for many who recur. Paclitaxel is also used by women diagnosed with breast cancer and off label for other cancers.

From the ASCO in ACTION website I learned:

June 23, 2011

Drug Shortages Legislation Introduced in the House
This week, Representatives Tom Rooney (R-FL) and Diana DeGette (D-CO) introduced H.R. 2245, legislation that would amend the Federal Food, Drug, and Cosmetic Act to provide the Food and Drug Administration (FDA) with improved capacity to prevent drug shortages. As an important first step in addressing the complex issue of drug shortages, this bill is consistent with recommendations from the November 2010 Drug Shortages Summit co-convened by ASCO. The proposed legislation includes provisions that would expand FDA authority to require manufacturer notification of shortages and market withdrawals, and enhance communication among health care providers and stakeholders in the pharmaceutical supply chain about the nature and expected duration of shortages. ASCO and the Summit co-conveners provided input on this legislation and have sent letters to the sponsors thanking them for taking action on this issue and in support of the legislation.

I am happy that some action is being taken by Congress to address this issue that effects cancer patients throughout the country.

Carboplatin and Paclitaxel are just two drugs on this list. There are other chemotherapy drugs listed as well. Will lives be lost due to this drug shortage? How much worse will the impact be on patients treated at small chemo clinics?How many patients will have their treatment delayed or switched? What about Taxol? Why is there not a shortage of the name brand?

Let us hope that manufacturing rates increase in the near future.

Dee

Every Day is a Blessing!