Cisplatin for brain mets

[psc]

My mother completed six cycles of weekly paclitaxel in Feb 09 and has been on Tykerb for almost a year now. Lately she has been complaining of drowsiness and weakness in her left leg. We got the brain MRI done - it shows multiple mets. Her oncologist said that radiation will not be an option since she has already taken radiation last year in July. He said we could give her Cisplatin infusion for 4 days in a row. This may help. We are very worried and dont know what to do.
1) Is it true that you cannot repeat radiation if you already had that before
2) Is Cisplatin recommended for brain mets, has anyone tried that.
Please share your experiences. Are there any other treatment options?
Please help,
thanks a lot,
psc
Dx Mom, Stage IV, ER- PR-, HER2+

[Sherryg683]

By radiation, do you mean she had whole brain radiation? Would gamma knife be an option for her, check into that...sherryg683

[psc]

Thanks Sherry. They are considering 3D conformal radiation for my mother. Has anyone tried that before?

thanks,
psc

[Jackie07]

Seems Cisplatin was used along with vinorelbine (injectable Novelbine). There is a chart in the middle of the info. provided at this site you might want to take a look:

http://www.drugs.com/pro/vinorelbine.html

[Jackie07]

Usage
Cisplatin is administered intravenously as short-term infusion in physiological saline for treatment of solid malignacies.

[edit] Cisplatin Resistance

Cisplatin combination chemotherapy is the cornerstone of treatment of many cancers. Initial platinum responsiveness is high but the majority of cancer patients will eventually relapse with cisplatin-resistant disease. Many mechanisms of cisplatin resistance have been proposed including changes in cellular uptake and efflux of the drug, increased detoxification of the drug, inhibition of apoptosis and increased DNA repair.[3]. Oxaliplatin is active in highly cisplatin-resistant cancer cells in the laboratory, however there is little evidence for its activity in the clinical treatment of patients with cisplatin-resistant cancer.[4] The drug Paclitaxel may be useful in the treatment of cisplatin-resistant cancer; the mechanism for this activity is unknown.[5]

[edit] Transplatin

Transplatin, the trans stereoisomer of cisplatin, has formula trans-[PtCl2(NH3)2] and does not exhibit a comparably useful pharmacological effect. Its low activity is generally thought to be due to rapid deactivation of the drug before it can arrive at the DNA.[citation needed] It is toxic, and it is desirable to test batches of cis-platin for the absence of the trans isomer. In a procedure by Woollins et al., which is based on the classic 'Kurnakov test', thiourea reacts with the sample to give derivatives which can easily be separated and detected by HPLC.[6]

[edit] Side effects

Cisplatin has a number of side-effects that can limit its use:

• Nephrotoxicity (kidney damage) is a major concern when cisplatin is given. The dose is reduced when the patient's creatinine clearance (a measure of renal function) is reduced. Adequate hydration and diuresis is used to prevent renal damage. The nephrotoxicity of platinum-class drugs seems to be related to reactive oxygen species and in animal models can be ameliorated by free radical scavenging agents (e.g., amifostine). This is a dose-limiting toxicity.
• Neurotoxicity (nerve damage) can be anticipated by performing nerve conduction studies before and after treatment.
• Nausea and vomiting: cisplatin is one of the most emetogenic chemotherapy agents, but this is managed with prophylactic antiemetics (ondansetron, granisetron, etc.) in combination with corticosteroids. Aprepitant combined with ondansetron and dexamethasone has been shown to be better for highly emetogenic chemotherapy than just ondansetron and dexamethasone.
• Ototoxicity (hearing loss): unfortunately there is at present no effective treatment to prevent this side effect, which may be severe. Audiometric analysis may be necessary to assess the severity of ototoxicity. Other drugs (such as the aminoglycoside antibiotic class) may also cause ototoxicity, and the administration of this class of antibiotics in patients receiving cisplatin is generally avoided. The ototoxicity of both the aminoglycosides and cisplatin may be related to their ability to bind to melanin in the stria vascularis of the inner ear or the generation of reactive oxygen species.
• Alopecia (hair loss): this does not generally affect patients treated with cisplatin.
• Electrolyte disturbance: Cisplatin can cause hypomagnesaemia, hypokalaemia and hypocalcaemia. The hypocalcaemia seems to occur in those with low serum magnesium secondary to cisplatin, so it is not primarily due to the Cisplatin.

[Jackie07]

Also, from another link:

Cisplatin is an antineoplastic medication. Cisplatin interferes with the growth of cancer cells and slows their growth and spread in the body.
Cisplatin is used to treat various types of cancer including metastatic testicular tumors, metastatic ovarian tumors, and advanced bladder cancer.
Cisplatin may also be used for purposes other than those listed in this medication guide.

[Jackie07]

Here's something about 3-D conformal radiation:

The goal of three-dimensional conformal radiation therapy is to surround the target with the prescribed radiation. In the past, radiation therapy plans were reviewed in a two-dimensional plane. The radiation dose above and below the plane was assumed adequate, but could not account for changes in the shape or contour of an organ or tumor.
Three-dimensional conformal radiation therapy accounts for the size, shape and mass of the tissues. A 3-D visualization allows the radiation oncologist to choose various radiation therapy beam arrangements to hit the tumor while minimizing the exposure to healthy tissue. Patient positioning is critical, so immobilization devices are routinely used.
*************************

It sounded like Gamma-knife Radiotherapy being applied to other parts of the body.

[Emmay]

My sister was on CPT-11(aka Irinotecan) + Avastin + Herceptin for a year; A year ago her MRI was very worrisome with multiple enhancing brain mets. After starting the above therapy, her 1st followup MRI looked dramatically improved, and the 2nd followup MRI looked clear of tumors, and stayed that way through March '09. She stopped CPT-11, and 6-8 wks later her MRI showed brain mets starting to grow again, so she may go back on CPT-11, possibly with another drug to address the torso mets...

Based on my sister's experience, I would highly recommend CPT-11+Avastin.

Emmay