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Welcome to Dr. Hamid Sanatinia's Virtual Headquarters
Testicular Cancer

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Chemotherapy for Testicular Cancer

BEP REGIMEN

Cisplatin 20 mg/m2 IV DAYS 1-5
Etoposide 100 mg/m2 IV DAYS 1-5
Bleomycin 30 units IV DAYS 2, 9, 16

REPEAT q21 days Total number of cycles varies.
Reduce etoposide by 20% with history of rediotherapy or fever with neutropenia after an earlier course.

CAUTION:
Cisplatin -- vigorous hydration is required; can be nephrotoxic and ototoxic; can cause peripheral neuropathy; hold or reduce for creatinine > 1.5

BLEOMYCIN: Give test dose of 1 - 2 units because of possible acute pulmonary, anaphylactoid, or severe febrile reactions; Dose-adjust for renal insufficiency; Total lifetime dose should not exceed 400 units; Avoid high FiO2

REF-JCO 16:1287, 1998
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VeIP
VINBLASTINE 0.11 mg / kg IV DAYS 1,2
IFOSFAMIDE 1200 mg / M2 / d CIV (120 hr) DAYS 1 - 5
CISPLATIN 20 mg / M2 IV DAYS 1 - 5
MESNA 400 mg / M2 IV DAY 1 - give bolus 15 minutes prior to Ifosfamide
Mesna 1200 mg / M2 / d CIV (120 hr) DAYS 1 - 5 start immediately after Mesna bolus

REF: Loehrer et al. Ann Intern Med 109:540, 1988
___________________________________________

EP

VP - 16 100 mg / M2 IV days 1 - 5
Cisplatin 20 mg / M2 IV days 1 - 5


REF-JCO 13:2700, 1995
___________________________________________

PVB
Cisplatin 20.00 mg / M2 IV days 1 - 5
VINBLASTINE 0.15 mg / kg IV days 1, 2
- reduce dose by 20% for prior radiotherapy
BLEOMYCIN 30 units IV days 2,9,16


REF:
NEJM 316:1436, 1987
Einhorn et al. Ann Intern Med 1977; 87:293 - 298
___________________________________________

VIP

CISPLATIN 20 mg/m2 IV
ETOPOSIDE 75 mg/m2 IV
IFOSFAMIDE 1,200 mg/m2 daily X 5 days

REF-JCO 16:1287, 1998
_____________________________________________________
VERY REFRACTORY PATIENTS/INTENSELY TREATED IN THE PAST

GEMCITABINE 1,000 mg/m2 IV infusion over 30 minutes once weekly for 3 consecutive weeks (days 1, 8, & 15), followed by a 1-week rest period.
Dose reduction 50% in the case of any grade 3 nonhematologic toxicity; Cessation of therapy in the case of grade 4 nonhematologic toxicity. For hematologic toxicity, 50% dose reduction in the case of thrombocytopenia (50,000 to 74,000/ÁL) or neutrophil counts between 500 & 1,000/ÁL.
REF: JCO 17(2): 512, 1999. RR=20%

Information on Bleomycin

Information on Etoposide

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TESTICULAR CANCER TREATMENT OPTIONS

--->NON-SEMINOMAS

------> CLINICAL STAGE A
ORCHIECTOMY
The overall relapse rate for these patients is approximately 30% (mostly retroperitoneum)
Several studies have shown that survival rate is similar to that of pathologic stage A.
Who may be at a higher risk of recurrence? Several histopathologic features of the primary tumor have been identified that are independently predictive of relapse in multivariate analysis. These include vascular invasion; lymphatic invasion; pathologic T stage higher than 1; the presence of components of embryonal carcinoma; percent of the primary tumor occupied by teratoma; & the presence or absence of yolk sac elements.
No chemotherapy!

------> PATHOLOGIC STAGE A
ORCHIECTOMY + RPLD
The overall relapse rate for these patients is approximately l0% (mostly lung)
5-year survival rates ~98%
The current recommendation for patients with pathologic stage A nonseminomatous disease is for no further therapy to be administered following RPLND. This recommendation is based on the high surgical cure rate with orchiectomy & RPLND alone (90%), the favorable relapse pattern in patients who recur (lung only), and the effectiveness of chemotherapy for small-volume metastatic disease in relapsing patients.
No chemotherapy!

------> PATHOLOGIC STAGE B
ADJUVANT CHEMOTHERAPY (BEP X 2)
Greater than 95% cure rate?

------> CLINICAL STAGE B2
If found to have nonbulky abdominal disease (nonpalpable, mass <5 cm on CT scan, or fewer than 5 nodes involved on CT scan), traditional therapy has included RPLND with complete resection, followed by either observation until relapse or adjuvant chemotherapy with excellent results.

------> CLINICAL STAGE B3
Not surgical candidate: palpable abdominal mass, lymph nodes > 5 cm, > 5 nodes involved on CT)
These patients must be treated with primary chemotherapy. After achievement of serological remission, complete restaging should be done & if any residual mass present, surgical removal is indicated.

AFP
Produced by: Fetal Yolk Sac; Embryonic carcinoma elements of germ cell tumors.
Overall, AFP is NOT elevated in pure seminomas.
Half-life: 5 days


B-HCG
Produced by: Trophoblastic tissues; Syncytiotrophoblastic components of of germ cell tumors.
Overall, B-HCG is NOT elevated in seminomas. However, about 10% of cases may have low-level elevation of B-HCG.
Half-life: 18-24 hours
There is some cross-reactivity in the radioimmunoassay with luteinizing hormone. Also, hCG can be falsely elevated in patients who use marijuana.

Stage Information



pTX: Primary tumor cannot be assessed (if no radical orchiectomy has been performed, TX is used.)
pT0: No evidence of primary tumor (e.g., histologic scar in testis)
pTis: Intratubular germ cell neoplasia (carcinoma in situ)
pT1: Tumor limited to testis and epididymis without lymphatic/vascular invasion
pT2: Tumor limited to testis and epididymis with vascular/lymphatic invasion, or tumor extending through the tunica albuginea with involvement of the tunica vaginalis
pT3: Tumor invades the spermatic cord with or without vascular/lymphatic invasion
pT4: Tumor invades the scrotum with or without vascular/lymphatic invasion

Regional lymph nodes (N)
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single lymph node, 2 cm or less in greatest dimension
N2: Metastasis in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, none more than 5 cm in greatest dimension
N3: Metastasis in a lymph node more than 5 cm in greatest dimension

Distant metastasis (M)
MX: Presence of distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis
M1a: Non-regional nodal or pulmonary metastasis
M1b: Distant metastasis other than to non-regional nodes & lungs

Serum tumor markers (S)
SX: Marker studies not available or not performed
S0: Marker study levels within normal limits
S1: LDH < 1.5 X N AND
HCG (mIu/ml) < 5000 AND
AFP (ug/ml) < 1000
S2: LDH 1.5-10 X N OR
HCG (mIu/ml) 5000-50,000 OR
AFP (ug/ml) 1000-10,000
S3: LDH > 10 X N OR
HCG (mIu/ml) > 50,000 OR
AFP (ug/ml) > 10,000
N: indicates the upper limit of normal for the LDH assay

AJCC stage groupings
Stage 0: pTis, N0, M0, S0
Stage I: pT1-4, N0, M0, SX
Stage IA: pT1, N0, M0, S0
Stage IB: pT2, N0, M0, S0 ; pT3, N0, M0, S0; pT4, N0, M0, S0
Stage IS: Any pT/Tx, N0, M0, S1-3
Stage II: Any pT/Tx, N1-3, M0, SX
Stage IIA: Any pT/Tx, N1, M0, S0; Any pT/Tx, N1, M0, S1
Stage IIB: Any pT/Tx, N2, M0, S0; Any pT/Tx, N2, M0, S1
Stage IIC: Any pT/Tx, N3, M0, S0; Any pT/Tx, N3, M0, S1
Stage III: Any pT/Tx, Any N, M1, SX
Stage IIIA:Any pT/Tx, Any N, M1a, S0 : Any pT/Tx, Any N, M1a, S1
Stage IIIB: Any pT/Tx, N1-3, M0, S2; Any pT/Tx, Any N, M1a, S2
Stage IIIC: Any pT/Tx, N1-3, M0, S3 ; Any pT/Tx, Any N, M1a, S3; Any pT/Tx, Any N, M1b, Any S

In addition to the clinical stage definitions, surgical stage may be designated based on the results of surgical removal and microscopic examination of tissue.

Stage I
Stage I testicular cancer is limited to the testis. Invasion of the scrotal wall by tumor or interruption of the scrotal wall by previous surgery does not change the stage but does increase the risk of spread to the inguinal lymph nodes, and this must be considered in treatment and follow-up. Invasion of the epididymis tunica albuginea and/or the spermatic cord also does not change the stage but does increase the risk of retroperitoneal nodal involvement and the risk of recurrence. This stage corresponds to AJCC stages I and II.

Stage II
Stage II testicular cancer involves the testis and the retroperitoneal or para-aortic lymph nodes usually in the region of the kidney. Retroperitoneal involvement should be further characterized by the number of nodes involved and the size of involved nodes. The risk of recurrence is increased if more than 5 nodes are involved, if the size of 1 or more involved nodes is larger than 2 centimeters, or if there is extranodal fat involvement. Bulky stage II disease describes patients with extensive retroperitoneal nodes (>5 centimeters) who require primary chemotherapy and who have a less favorable prognosis. This stage corresponds to AJCC stages III and IV (no distant metastasis).

Stage III
Stage III implies spread beyond the retroperitoneal nodes based on physical examination, x-rays, and/or blood tests. Stage III is subdivided into nonbulky stage III versus bulky stage III. In nonbulky stage III, metastases are limited to lymph nodes and lung with no mass larger than 2 centimeters in diameter. Bulky stage III includes extensive retroperitoneal nodal involvement, plus lung nodules or spread to other organs such as liver or brain. This stage corresponds to AJCC stage IV (distant metastasis).