Chapter 8 anticancer - antibiotic anticancer agents + mitosis inhibiors and platinum containing agents

Question 1

dactinomycin

s-phase specific

Answer 1

• intercalates between guanine bases of DNA
• dec RNA synthesis - via block DNA-dependent RNA synthesis

indication (IV agent)
1) wilm’s tumor (rare kidney cancer that mainly affects children. Also known as nephroblastoma, it’s the most common cancer of the kidneys in children. Wilms tumor most often affects children ages 3 to 4. It becomes much less common after age 5, but it can affect older children and even adults.

Wilms tumor mostly occurs in just one kidney. But it can sometimes be in both kidneys at the same time.)

2) ewings (Ewing (YOO-ing) sarcoma is a rare type of cancer that occurs in bones or in the soft tissue around the bones.

Ewing sarcoma most often begins in the leg bones and in the pelvis, but it can occur in any bone. Less often, it starts in the soft tissues of the chest, abdomen, limbs or other locations.

Ewing sarcoma is more common in children and teenagers, but it can occur at any age.)

3) rhabdomyosarcoma (Sarcoma is cancer of soft tissue (such as muscle), connective tissue (such as tendon or cartilage), or bone. Rhabdomyosarcoma usually begins in muscles that are attached to bones and that help the body move, but it may begin in many places in the body.)

4) testicular tumors

Question 2

doxorubicin (adriamycin)
daunorubicin
idarubicin
epirubicin

s phase specific

Answer 2

• anthracycline chemical structure
• intercalate into DNA (dec RNA / DNA synthesis via, cause DNA strand breaks via topoisomerase II)

effect
* Irreversible cardiomyopathy (problems with your heart muscle that can make it harder for your heart to pump blood)
* this risk can be reduced by slowing infusion and capping lifetime exposure
2) cause radiation recall — previously irradiated skin/tissue becomes inflamed

ultimately – these IV agents used in combination with other drugs for various types of cancers

Question 3

Bleomycin

g2/M phase specific

Answer 3

• bithizole rings intercalate into DNA strand
• Drug oxidizes iron ==> creating free radical that damage DNA

Effect
* notable one — pulmonary fibrosis (thickening or scarring of the tissue. In this case, the normally thin, lacy walls of the air sacs in the lungs are no longer thin and lacy, but get thick, stiff and scarred, also called becoming fibrotic.)
* TEST DOSES GIVEN TO TEST FOR ANY ANAPHYLACTIC RXN’s

• combination therapies d/t being less immunosuppressive than other cytotoxic agentes

indicated
1) testicular cancer
2) squamous cell head and neck cancer
3) lymphomas (cancer that begins in cells of the lymph system.)

Question 4

mitoxantrone (novantrone)

not phase specific

Answer 4

• inhibit DNA + RNA synthesis
• causes DNA breaks via stopping toposiomerase II

indication
* IV agent for acute non-lymphocytic leukemia

Question 5

pilcamycin

not phase specific

Answer 5

• blocks DNA polymerase
• does not intercalate…

indication
* slow IV infusion for metastatic testicular tumors

Question 6

mitomycin C

not phase specific

Answer 6

• metabolzied to an alkylating and crosslinking agent (prodrug)

indication
* IV drug for
1) adenocarcinoma (develops in the glands that line your organs. Common forms of adenocarcinoma include breast, stomach, prostate, lung, pancreatic and colorectal cancers.) of the stomach, colon, pancreatic, and breast cancer
2) squamous cell head and neck carcinoma

Question 7

Vincristine (oncovin)
vinblastine
vinorebine

vinca alkyloid

Answer 7

• m-phase specific agent
• binds tubilin => depolarize microtubules
• vinblastine + vinorelbine (both same mech)

indication
* leukemia
* lymphoma
* solid tumors (some)
///
vinorebine (same as top), including non-small cell lung cancer, breast, ovarian, hodgkins (Non-Hodgkin lymphoma may arise in lymph nodes anywhere in the body, whereas Hodgkin lymphoma typically begins in the upper body, such as the neck, chest or armpits. Hodgkin lymphoma tends to progress in a more predictable way than non-Hodgkin lymphoma, making it easier to recognize and treat.)

effects
* neuropathy
* jaw pain
* minimal bone suppression
/////
vinblastine –
* less neuropathy BUT more bone suppression
/////
vinorebine –
* less neurotoxicity d/t decreased affinity for nerve tubules

Question 8

paclitaxel (taxol)

taxanes

Answer 8

• M-phase specific
• stabilize microtubules and prevent depolymerization that is necessary for mitosis

indication
* metastatic ovarian carcinoma
* breast cancer

effects
* peripheral neuropathy
* marrow suppression
* myalgias (pain in muscle)
* hypersen rxn

Question 9

albumin-bound paclitaxel (abraxane)

taxane

Answer 9

this combo, toxicity inducing solvents in paclitaxel (by itself) are moved which improved therapeutic index

indication
* metastatic breast cancer

Question 10

Docetaxel (taxotere)
Cabazitaxel (jevtana)

taxane

Answer 10

• M-phase specific
• stabilize microtubules and prevent depolymerization that is necessary for mitosis
• both similar to paclitaxel !!!!
• **Cabazitaxel **(better penetration via BBB than paclitaxel)

indication
* metastatic ovarian carcinoma
* breast cancer

effects
* peripheral neuropathy (less in docetaxel)
* marrow suppression
* myalgias (pain in muscle)
* hypersen rxn

Question 11

etoposide (VePesid)
teniposide (vumon)

topoisomerase inhibitors

Answer 11

• g2 phase specific drug
• interefer w/ topoisomerase => cause DNA breaks
• teniposide similar to etoposide in mech

indication
* testicular cancer
* lung cancer
* teniposide — leukemia in children!

effects
* marrow suppression
* mucositis ( mouth or gut is sore and inflamed, painful)
* nasuea
* hypotension d/t rapid infusion

Question 12

topotecan (hycamptin)
irinotecan (camtosar)

topoisomerase inhibitors

Answer 12

• interact w/ topoisomerase I
• l/t DNA strand break during replication
• irinotectan (similar to topotecan)

indication:
* lung and ovariran carcinoma
* Topotecan — metastatic colon carcinoma

effects
* marrow suppression
* irinotecan (severe diarrhea)

Question 13

ixbepilone (ixempra)

epothilones

Answer 13

• promotes tubulin polymerization

Indication (IV drug)
* metastatic breast cancer resistant to anthracyline (AB anti cancer drug) and taxane therapy

Question 14

clisplantin (platinol-AQ)
carboplatin (paraplatin)
oxaliplatin (eloxatin)

platinum containing agents

Answer 14

• mech unclear
• carboplatin + oxaliplatin both similar to clisplantin

indication
* metastatic testicular atumor
* ovarian tumor
* advanced bladder cancer
* some CNS tumor
* Carboplatin (equal in efficacy for lung + ovarian cancer; overall less effective than cisplatin)
* **Oxaliplatin **(improved efficacy for advanced colorectal cancer + used in combination therapy)

effect
irreversible ototoxicity
nephrotoxicity

IV drug — clisplantin (penetrates testes barrier and partially penetrates BBB