Cancer Drugs & Chemotherapeutic Agents: Dactinomycin, Doxorubicin, Bleomycin etc. – White Blood Cell Pathology

by Carlo Raj, MD

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    00:02 We have a drug here called dactinomycin.

    00:04 You’d find that children might be acting out, so you’re looking at childhood cancers.

    00:08 It intercalates the DNA, making it difficult for the DNA to properly carry its action.

    00:14 So once you know it’s childhood cancers that you’re affecting, then you start thinking about the childhood cancers, Wilms tumor, the renal cell cancer in your child, Ewing’s sarcoma.

    00:25 This is your translocation that you know about called 11;22, and you have involvement at the diaphysis of the bone in Ewing’s sarcoma.

    00:34 Rhabdomyosarcoma, especially the young type, and you’re referring to embryonal rhabdomyosarcoma, a.k.a. sarcoma botryoides, usually used for childhood tumors.

    00:47 Myelosuppressions, what are you looking for? Doxorubicin, Adriamycin.

    00:51 Here, it generates free radicals, noncovalently intercalated DNA, breaks into DNA, and also inhibits replication.

    01:01 So there are many points of your proper DNA mechanism or replication that completely slows it down.

    01:07 The clinical uses: part of what’s known as ABVD, and this is your Adriamycin, which is part of regimen that you probably need to know for Hodgkin.

    01:16 Also, used for myelomas, solid tumors, a lot of places.

    01:21 In the process though, what you’re worried about definitely is cardiotoxicity, dilated cardiomyopathy, marked alopecia, and toxic tissue because of extravasation.

    01:33 It actually comes out, cause damage to the tissue.

    01:36 Doxorubicin, Adriamycin, ABVD, Hodgkin.

    01:41 Bleomycin, a G2 phase inhibitor, specifically, includes a formation of free radicals.

    01:48 Again, just like we saw with your doxy, and it breaks your DNA strand.

    01:53 Can use this in testicular cancer.

    01:55 It’s also part of your ABVD.

    01:57 The B in ABVD is your bleomycin.

    02:01 The A was Adriamycin, which is part of that doxorubicin.

    02:04 Well, bleomycin, it may then cause pulmonary fibrosis, B and B, if that helps you.

    02:10 Also, myelosuppression.

    02:12 There, etoposide, or toposide, in general; teniposide and etoposide.

    02:16 teniposide and etoposide.

    02:18 Well, these are the drugs that then inhibit topoisomerase 2.

    02:21 Therefore, it increases DNA degradation.

    02:24 It’s used between S and G2.

    02:27 It can be used for small cell lung cancer, which is also called oat cell.

    02:31 If you want, take a look at the ETO in etoposide.

    02:34 How would you pronounce OTE? Oh, ote, if that helps you.

    02:39 So etoposide, oat cell cancer.

    02:42 What’s another name for small cell? Oh, yes, oat cell cancer of the lung.

    02:47 Also, testicular and prostate, and you’re worried about alopecia and myelosuppression, etoposide, topoisomerase 2, oat cell cancer of the lung, and testicular.

    02:57 Cyclophosphamide, ifosfamide, covalently X-linked.

    03:04 You need to memorize guanine N-7.

    03:07 Bioactivation by the liver.

    03:10 Non-Hodgkin’s lymphoma, hemorrhagic cystitis, look for blood in the urine, and maybe treated by giving mesna.

    03:21 Know your couple of rescues, please.

    03:23 Mesna, leucovorin.

    03:26 Nitrosourea: You have carmustine, lomustine, semustine, lustines, requires bioactivation.

    03:37 This, you need to make sure C –, carmustine, C – crosses the blood-brain barrier into the CNS.

    03:45 Therefore, brain tumors, including GBM, glioblastoma multiforme.

    03:52 Is it always effective? Unfortunately, it’s not.

    03:55 May then, unfortunately, because of its crossing, cause CNS toxicity.

    04:02 Busulfan: alkylates the DNA.

    04:06 CML, also used for ablating bone marrow in hematopoeietic stem cell transplantation.

    04:13 Don’t forget about that.

    04:13 That’s big.

    04:15 And here, once again, another B, busulfan, pulmonary fibrosis.

    04:20 What was the other one that start with the B resulting in pulmonary fibrosis? Very good.

    04:25 We had our bleomycin.

    04:31 Here, we have our vinca alkaloids.

    04:34 So, we’re in the M phase.

    04:35 Vincristine and vinblastine.

    04:38 Use the -cristine and the -blastine to advantage.

    04:41 You’ll see why.

    04:43 Mechanism, what does it do? Well, in the M-phase, it literally inhibits the polymerization of your microtubule.

    04:50 And therefore, the microtubules will not properly pull your chromosomes apart.

    04:56 That’s your vinca alkaloid.

    04:58 It’s part of your MOPP regimen for Hodgkin, and this would then be oncovin, which is your vincristine.

    05:06 Also, it could be used for choriocarcinoma, vincristine.

    05:11 Toxicity.

    05:12 Okay, the C in vincristine will be for CNS toxicity.

    05:18 Also, oncovin, also choriocarcinoma, CCC.

    05:24 If you’re dealing with vinblastine, it’s going to affect the bone marrow.

    05:29 B – blastine, B – bone marrow suppression.

    05:34 Vinca alkaloids.

    05:37 Taxol, another method in which you can affect the M phase.

    05:42 Here, literally, the spindle is not going to break down.

    05:45 You’re going to inhibit taxing.

    05:48 You can use this for, perhaps, ovarian and breast cancers in a female, obviously.

    05:52 And hypersensitivity is what you’re looking for.

    05:55 The paclitaxel and vinca alkaloids will be affecting your M phase.

    06:00 Don’t forget though, the vinca alkaloids will behave by inhibiting the polymerization.

    06:04 And then here, it will hyperstabilize the taxols, will hyperstabilize the polymerized microtubule.

    06:11 In other words, it will freeze the “tubules” so that it doesn’t break down, therefore, cannot replicate.

    06:20 Make sure that you know the actual medical pharmacologic language when dealing with vinca alkaloids, and also, taxols.

    06:28 Hyperstabilization, inhibition of polymerization.

    06:33 Cisplatin, carboplatin, plat-, your platinum drugs.

    06:38 Cross-link DNA.

    06:40 Testicular cancer, ovarian cancer.

    06:44 Acoustic, acoustic nerve damage, eighth cranial nerve, platin.

    06:51 Hydroxyurea: Last time you saw hydroxyurea was to then inhibit what’s known as -- or to help a patient increase your hemoglobin F.

    07:02 It inhibits ribonucleotide reductase.

    07:05 Memorize ribonucleotide reductase, hydroxyurea.

    07:09 Next, it is used and could be used for melanoma, CML.

    07:14 And the reason we have sickle disease, even though it’s not a cancer is the fact that it increases hemoglobin F.

    07:21 In sickle cell disease, remember your completely deficient hemoglobin A, you’re then going to increase quite a bit of hemoglobin S when you have polymerization.

    07:31 This is not good.

    07:32 You are then going to or wish to increase hemoglobin F, which will then cause a left shift.

    07:38 This is then going to also cause bone marrow suppression and GI upset.

    07:44 Here, we have prednisone.

    07:45 What is a steroid doing here? Well, it may trigger apoptosis, as we know.

    07:50 Remember, the lymphopenia stuff that we talked about earlier.

    07:54 It may even work on non-dividing cells.

    07:56 Most common glucocorticoid in cancer therapy used in CLL, chronic lymphocytic leukemia.

    08:02 May be part of that MOPP regimen, your last P.

    08:06 We have also immunosuppressed.

    08:08 Meaning to say that it may be used in autoimmune diseases, which then require immunosuppression.

    08:13 Obviously, when utilizing prednisone, you’re worried about Cushing-like symptom, cataract, osteoporosis, everything that you would expect with prednisone or cortisol type of side effect, including your peptic ulcer disease in the stomach.

    08:28 Here, we have our tamoxifen and raloxifene.

    08:32 First and foremost, these are going to be your estrogen receptor modulators.

    08:37 These are then going to behave as antagonist in the breast and agonist in the bone.

    08:41 So therefore, these are partial agonists.

    08:44 It will block the binding of estrogen to the estrogen receptor-positive cells.

    08:49 You’re looking at your ER positive breast cancers.

    08:53 Also, osteoporosis because it is going to be an agonist towards your bone.

    08:58 We’re going to divide our tamoxifen, raloxifene as such.

    09:01 Tamoxifen may increase the risk of endometrial cancer due to the partial agonist type of effective estrogen.

    09:08 Whereas, raloxifene does not increase the risk of endometrial cancer because it is an endometrial antagonist.

    09:16 Raloxifene seems to be a little bit better in terms of not having as much of a risk as tamoxifen.

    09:23 Here, we have Herceptin or trastuzumab.

    09:26 Your patient is HER-2/neu positive, which is Erb-B2.

    09:29 HER-2 stands for human epidermal receptor growth factor.

    09:34 This is a metastatic breast cancer or really, really Erb-B2 positive, extremely, extremely dangerous breast cancer, extremely cardiotoxic.

    09:44 Imatinib would be used for 9 and 22.

    09:48 We talked about tyrosine kinase.

    09:50 It could also be used forth on a c-kit positive, or CD117.

    09:55 And by c-kit, we mean that also, you’ve heard of gastrointestinal stromal tumor, and you could have tyrosine kinase there as well.

    10:02 And so therefore, imatinib would be a drug to utilize in such issues.

    10:06 CML and GIST, gastrointestinal stromal tumor, which is a smooth muscle benign tumor found in the stomach.

    10:16 Rare, but of all the benign tumors in the stomach, GIST is the most common.

    10:21 Fluid retention toxicity.

    About the Lecture

    The lecture Cancer Drugs & Chemotherapeutic Agents: Dactinomycin, Doxorubicin, Bleomycin etc. – White Blood Cell Pathology by Carlo Raj, MD is from the course Leukemia – White Blood Cell Pathology (WBC).

    Included Quiz Questions

    1. Doxorubicin
    2. Bleomycin
    3. Etoposide
    4. Dactinomycin
    5. Cyclophosphamide
    1. Chronic myelogenous leukemia
    2. Metastatic breast cancer
    3. Hodgkin’s lymphoma
    4. Melanoma
    5. Lung carcinoma
    1. Bleomycin
    2. Etoposide
    3. Cyclophosphamide
    4. 5-fluorouracil
    5. Dactinomycin
    1. Alkylates DNA
    2. Intercalate in DNA
    3. Inhibits reductase
    4. Inhibits topoisomerase II
    5. Free radical formation
    1. Prednisone
    2. Beclomethasone
    3. Betamethasone
    4. Budesonide
    5. Cortisone

    Author of lecture Cancer Drugs & Chemotherapeutic Agents: Dactinomycin, Doxorubicin, Bleomycin etc. – White Blood Cell Pathology

     Carlo Raj, MD

    Carlo Raj, MD

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