Tx of Testicular Cancer

Question 1

Question 2

How is testicular cancer staged?

Answer 2

Stage I: cancer found only in the testicle

Stage II: Cancer has spread to the lymph nodes in the abdomen

Stage III: Cancer spread beyond the abdominal lymph nodes (lung, liver, brain, bones)

Question 3

T or F. Testicular cancer represents the most common solid tumor in young men

Answer 3

T. However, it can be well managed and is very chemo-sensitive

95% are germ cell tumors arising in the testes (classified as seminoma or nonseminoma)

Question 4

What are the risk factors for testicular cancer?

Answer 4

personal of family Hx., cryptorchidism, testicular dysgenesis, or Klinefelter syndrome

Question 5

What are some serum markers for testicular cancer?

Answer 5

Alpha-fetoprotein, LDH, and B-human chorionic gonadotropin (B-HCG)

Question 6

What are the tx options for testicular cancer?

Answer 6

Surgery is usually curative for confined cancer (and removal of one testes doesnt have a significant effect on fertility). For disease that has begun to metastasize to abdominal lymph, radiotherapy and/or chemo is used adjunctively. In general, seminomas grow slow.

Question 7

What are the chemo options for testicular cancer?

Answer 7

All options invovle a platinum drug. Note that although cisplatin is very effective, it loses effectiveness with repeated used

Question 8

How do cancer cells lose sensitivity to cisplatin?

Answer 8

As a result of a wide panel of genetic or epigenetic defects that can (i) affect that preced the binding of cisplatin (pre-binding resistance), (ii) potentiate the ability to repair cisplatin induced damage, (iii) impair cisplatin signal tranduction or (iv) stimulate signals that antagonize cisplatin cytotoxicity

Usually a combination of these things are in play

Question 9

How does Bleomycin work?

Answer 9

binds DNA in the presence of iron to mediate DNA strand breakage

Question 10

How does Etoposide work?

Answer 10

stabilizes DNA and topo II complexes resulting in strand breakage

Question 11

How does Ifosfamide work?

Answer 11

It is a metabolically-activated alkyalting agent producing intra and interstrand DNA cross-linked (mesna can be protective against drug induced hemorrhagic cystitis)

Question 12

AEs of Bleomycin?

Answer 12

Dose-limiting pulmonary fibrosis and interstitial pneumonitis

late developing skin toxicity (striae, hyperpigmentation, pruritus)

Question 13

AEs of Cisplatin?

Answer 13

Dose-limiting renal toxicity (renally eliminated and accumulaiton can occur)- give amifostine

neuro and ototoxicity in higher doses (cochlea damage via ROS generation via copper transporter)

Question 14

AEs of Carboplatin?

Answer 14

Dose-limiting thrombocytopenia

some neuro, oto, and nephrotoxicity

Question 15

AEs of Etoposide

Answer 15

Dose-limiting leukopenia

hepatic toxicity

Question 16

AEs of Ifosfamide?

Answer 16

Dose-limiting myelosuppression

neurotoxicity (coma, seizures, ataxia from chloroacetaldehyde release)

Question 17

AEs of Paclitaxel?

Answer 17

Dose-limiting bone marrow suppression (Filgastrim protective)

peripheral neuropathy, especially in diabetics

Question 18

AEs of Vinblastine?

Answer 18

Dose-limiting neuropathy

Question 19

How does Cisplatin work?

Answer 19

In addition to binding to nuclear DNA, it can interactwith mitochondrial DNA and proteins to promote ROS and elicit signal transduction to promote BCL-2 induced cell apoptosis, as well as activating p53

Question 20

How can the ototoxicity associated with cisplatin be avoided?

Answer 20

Co-administration of antioxidants early in treatment

Question 21

How can the nephrotoxicity associated with cisplatin be avoided?

Answer 21

Since cisplatin tends to accumulate in renal cells via several transporters, including OCT2 (whose expression is generally restricted to few cells such as renal, cochlear, and nervous cells, while its expression in some tumors seems to be epigenetically down-regulated) inhibition of this transporter may be effective in decreasing cisplatin uptake in non-target cells without affecting its ability to target tumor cells

Question 22

How does bleomycin cause lung injury?

Answer 22

Bleo can injure lung epithelial cells and can stimulate the production of ROS that enhance recruitment of immune modulators that can induce more damage

Question 23