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Just something I found in my feeds…The efficacy of temozolomide( Temodar) in melanoma treatment is low (response rate <20%)

Forums General Melanoma Community Just something I found in my feeds…The efficacy of temozolomide( Temodar) in melanoma treatment is low (response rate <20%)

  • Post
    LynnLuc
    Participant

    Posting this because in the beginning I  was on this and I knew it didn't hold mine back for long…the radiation did more then Temodar did…

    Temozolomide chemoresistance heterogeneity in melanoma with different treatment regimens: DNA damage accumulation contribution.

    Posting this because in the beginning I  was on this and I knew it didn't hold mine back for long…the radiation did more then Temodar did…

    Temozolomide chemoresistance heterogeneity in melanoma with different treatment regimens: DNA damage accumulation contribution.

    The efficacy of temozolomide in melanoma treatment is low (response rate <20%) and may depend on the activity of O-methylguanine DNA methyltransferase (MGMT) and mismatch repair. We identified melanoma cell lines with different sensitivities to single versus prolonged clinical dosing regimens of temozolomide treatment and assessed a variety of potential resistance mechanisms using this model. We measured mRNA expression and promoter methylation of MGMT and essential mismatch repair genes (MLH1, MSH2). Cell cycle distribution, apoptosis/necrosis induction, O-methylguanine-adduct formation, and ABCB1 gene expression were assessed. We found that three cell lines, MelA, MelB, and MelC, were more sensitive to a single dose regimen than to a prolonged regimen, which would be expected to exhibit higher cytotoxicity. KAII and LIBR cell sensitivity was higher with regard to the prolonged treatment regimen, as expected. Only MelC expressed MGMT. Gene expression correlated well with promoter methylation. Temozolomide exposure did not alter mRNA expression. Different sensitivities to temozolomide were caused neither by delayed apoptosis induction due to early cell cycle arrest nor by O-methylguanine-adduct formation or efflux transporter expression. MelC was the most resistant cell line with rapid elimination of O-methylguanine adducts. This was in good agreement with its MGMT expression. The sensitive cell lines KAII and LIBR accumulated O-methylguanine adducts after a second treatment cycle with temozolomide in contrast with the other three cell lines. We conclude that MGMT expression and DNA adduct accumulation are relevant factors in temozolomide chemosensitivity. Considering individualized temozolomide treatment regimens either by quantification of DNA adducts or by chemosensitivity testing seems worthwhile clinically.

    http://www.curehunter.com/public/pubmed21460749.do

    May 26th will be 14 months NED

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  • Replies
      nicoli
      Participant

      Well, ya gotta admit………. most of our treatments are 20% more or less. Not much out there.

      Are you saying that you think radiation kept your cancer away better than temador?

      Please say so, I am doing radiation now to prevent another recurrence and I need all the encouragement I can get!

      Nicki, Stage 3b, scalp

      nicoli
      Participant

      Well, ya gotta admit………. most of our treatments are 20% more or less. Not much out there.

      Are you saying that you think radiation kept your cancer away better than temador?

      Please say so, I am doing radiation now to prevent another recurrence and I need all the encouragement I can get!

      Nicki, Stage 3b, scalp

        FormerCaregiver
        Participant

        That is an interesting question that you raise regarding the efficacy of radiation compared to a
        chemo drug such as temador. Radiotherapy is normally a localised treatment, whereas chemo is
        usually systemic (involves the whole body). Comparisons can be difficult because of this.

        I have read your profile and I am wondering if you know the depth of your primary? This is
        important because this depth of your initial lesion will usually give us good idea of your
        overall situation.

        You are in my prayers.

        Frank from Australia

        nicoli
        Participant

        Ya talking to me, Frank?

        Course I know the depth of my primary, just too lazy to look it up the day I did the profile. Breslow depth 1.82 mm.  Clark's Level IV. Nodular ulcerated. Mitotic index a whopping 18.

        Hey, I was remembering that someone ( I think maybe you) mentioned some kind of injection directly into a tumor. Is this something available in Australia? Wonder if available in US?

        Also, did you mention something with a response rate of 80%?

        As for the radiation, I am doing localized to hopefully prevent future recurrences. I have tried biochemo and interferon, with no response. At this point, we think tumors are gone and are now just mopping up cells. 

        Nicki, Stage 3b, scalp 

        nicoli
        Participant

        No true. The 1.82 was the initial biopsy. The wle revealed an additional depth of 2.05. Makes a total depth of 3.87.

        Nicki, Stage 3b, scalp

        FormerCaregiver
        Participant

        Yes, I was and thanks for your response Nicki. So, the actual depth of your primary was 3.87 mm.
        Thank you for clarifying that and for updating you profile. I feel that as it is under 4 mm, the
        melanoma cells are less likely to spread throughout the bloodstream and will probably remain in
        the lymph system.

        I think that you might be thinking about Rose Bengal (PV-10). They have been doing trials with it
        here and elsewhere, and it seems to be effective in many cases. However, what that means is yet
        to be fully determined.

        Here is an old video about it:
        http://www.youtube.com/watch?v=HSjoev_q9Nw

        This is a link to the company's website:
        http://www.pvct.com/

        Best wishes

        Frank from Australia

        FormerCaregiver
        Participant

        Yes, I was and thanks for your response Nicki. So, the actual depth of your primary was 3.87 mm.
        Thank you for clarifying that and for updating you profile. I feel that as it is under 4 mm, the
        melanoma cells are less likely to spread throughout the bloodstream and will probably remain in
        the lymph system.

        I think that you might be thinking about Rose Bengal (PV-10). They have been doing trials with it
        here and elsewhere, and it seems to be effective in many cases. However, what that means is yet
        to be fully determined.

        Here is an old video about it:
        http://www.youtube.com/watch?v=HSjoev_q9Nw

        This is a link to the company's website:
        http://www.pvct.com/

        Best wishes

        Frank from Australia

        nicoli
        Participant

        No true. The 1.82 was the initial biopsy. The wle revealed an additional depth of 2.05. Makes a total depth of 3.87.

        Nicki, Stage 3b, scalp

        nicoli
        Participant

        Ya talking to me, Frank?

        Course I know the depth of my primary, just too lazy to look it up the day I did the profile. Breslow depth 1.82 mm.  Clark's Level IV. Nodular ulcerated. Mitotic index a whopping 18.

        Hey, I was remembering that someone ( I think maybe you) mentioned some kind of injection directly into a tumor. Is this something available in Australia? Wonder if available in US?

        Also, did you mention something with a response rate of 80%?

        As for the radiation, I am doing localized to hopefully prevent future recurrences. I have tried biochemo and interferon, with no response. At this point, we think tumors are gone and are now just mopping up cells. 

        Nicki, Stage 3b, scalp 

        FormerCaregiver
        Participant

        That is an interesting question that you raise regarding the efficacy of radiation compared to a
        chemo drug such as temador. Radiotherapy is normally a localised treatment, whereas chemo is
        usually systemic (involves the whole body). Comparisons can be difficult because of this.

        I have read your profile and I am wondering if you know the depth of your primary? This is
        important because this depth of your initial lesion will usually give us good idea of your
        overall situation.

        You are in my prayers.

        Frank from Australia

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