How is testicular cancer staged?
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)
T or F. Testicular cancer represents the most common solid tumor in young men
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)
What are the risk factors for testicular cancer?
personal of family Hx., cryptorchidism, testicular dysgenesis, or Klinefelter syndrome
What are some serum markers for testicular cancer?
Alpha-fetoprotein, LDH, and B-human chorionic gonadotropin (B-HCG)
What are the tx options for testicular cancer?
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.
What are the chemo options for testicular cancer?
All options invovle a platinum drug. Note that although cisplatin is very effective, it loses effectiveness with repeated used
How do cancer cells lose sensitivity to cisplatin?
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
How does Bleomycin work?
binds DNA in the presence of iron to mediate DNA strand breakage
How does Etoposide work?
stabilizes DNA and topo II complexes resulting in strand breakage
How does Ifosfamide work?
It is a metabolically-activated alkyalting agent producing intra and interstrand DNA cross-linked (mesna can be protective against drug induced hemorrhagic cystitis)
AEs of Bleomycin?
Dose-limiting pulmonary fibrosis and interstitial pneumonitis
late developing skin toxicity (striae, hyperpigmentation, pruritus)
AEs of Cisplatin?
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)
AEs of Carboplatin?
some neuro, oto, and nephrotoxicity
AEs of Etoposide
AEs of Ifosfamide?
neurotoxicity (coma, seizures, ataxia from chloroacetaldehyde release)
AEs of Paclitaxel?
Dose-limiting bone marrow suppression (Filgastrim protective)
peripheral neuropathy, especially in diabetics
AEs of Vinblastine?
How does Cisplatin work?
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
How can the ototoxicity associated with cisplatin be avoided?
Co-administration of antioxidants early in treatment
How can the nephrotoxicity associated with cisplatin be avoided?
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
How does bleomycin cause lung injury?
Bleo can injure lung epithelial cells and can stimulate the production of ROS that enhance recruitment of immune modulators that can induce more damage