germ cell tumors germ cell tumors- biology - Plataforma de Oncología

GERM CELL TUMORS
International Germ Cell Prognostic Factors (JCO 1977;15:594-603)
Good Seminoma Non Seminoma
90% of tumors 56% of tumors
5yPFS 82%; 5yOS 86% 5yPFS 89%; 5yOS 92%
Any site; only lung mets Testes, retroperitoneum, only lung mets
AFP normal, any BHCG, AFP10xN
GERM CELL TUMORS- BIOLOGY
RSK Chaganti et al (Ca Res 2000;60:1475-82). Common features: Cyclin D2 overexpression, bax>bcl2
(propapotosis), and wt p53.
J Hartmann et al (C Bokemeyer, Univ Tubingen) (JNCI 2000;92:54-61). Primary germ cell tumors of the
mediastinum and hematological disorders. N=635. Observed 17 MDS and AL, all with non seminomatour
GCT. HR=250 compared to normal population. MT to hematological disorder diagnosis 6mo. MST 5 mo.
LS Travis et al (JNCI 2000;92:1165-71). Leukemia risk after GCT therapy (15 year F up).24/10000 patients.
Benefit outweigh risk for RT or Pt based ChX.
J Hartmann (JNCI 2001;93:1733-8). Incidence of testes tumor after extragonadal GCT 4.1%. (SIR =62).
R De Witt and K Fizazi (JCO 2006;24:5482-92). Stage I seminoma.:

D Sharp et al MSKCC (JCO 2008;26:5524-9). Incidence of late recurrences in the literature 3.2% in non
seminomatous and 1.4% in seminoma. Frequent in non operated retroperitoneal mets. MSKCC series 75
patients, interval 2.1-37.7 years. Complete resection 5yOS 79%, vs non completely resected 36%. Better for
untreated patients.
E de Haas et al (JCO 2008;26:2817-23). Bleomycin hydrolase gene SNP A1450G homozygous G/G worst
survival as compared t6o heterozygous A/G and wt A/A. Series of 31, 133 and 140 patients respectively.
HR=4.97. Differences in OS at 20y were 90% vs 60%.
BS Carver et al MSKCC (JCO2007;25:1033-7). Tweratoma found in 40% postchemotherapy RPLND. Series
of 210 patients with teratoma: mature 85%, with malignant transformation 8%, and with inmature teratoma
8%. M F up 37 mo: 5yDFS 83% and 10yDFS 80%. Recurrences were: 10 teratoma, 5 with malignant
transformation and 15 (50%) with GCT.
GERM CELL TUMORS – ADJUVANT THERAPY
P Albers et al (JCO 2008;26:2966-72). N=382 stage I NSGCT, postorchidectomy, MF up 4.7y. Randomized
to RPLND (15 recurrences/191; 2yRFS 91.8%, HR=7.9) vs BEPx1 (2 recurrences/191; 2yRFS 99.4%).
GERM CELL TUMORS – ADVANCED DISEASE
BEP: Bleo is an essential component (10% OS gain, Indiana randomized trial).
VIP
VeIP (only 10% long term survivors)
BEP va CEP (CBDCA inferior to CDDP) (Randomized German, EORTC trials)
BEP = VIP (Intergroup USA)
BEP x 3 =BEP x 4
POMP�EPI in poor prognosis group (2yPFS 58%)
TXL-IFX-CDDP second line (OR 80%).
GEM active second line
S Hinton et al (L Einhorn) (JCO 2002;20:1859-63). N=28 refratory. TXL 110 mg/m2 d 1, 8 & 15 + GEM
1000 mg/m2 d 1, 8, & 15 q 4 wk x 6. OR 21.4% (3 CR NED 15+ to 25+ mo).
T Miki et al Osaka (Cancer 2002;95:1879-85). N=20 refractory. CPT 150 mg/m2+CDDP 20 mg/m2 x 5 d.
OR 50% 5yOS 53%. Active salvage therapy.
C Kollmannsberger et al (C Bokemeyer). (JCO2004;22:108-114). N=35, refractory, 89% recerrence after
BMT. GEM 1000 mg/m2 d 1 & 8 + LOHP 130 mg/m2 d 1 q 4 wk. OR 46%, CR 3. CDDP refratory OR 44%.
B Cushing et al POG-CCG (JCO 2004;22:2691-700). N=299, children. Randomized to BEP conventional
(CDDP 20 mg/m2x 5) (6yEFS 80%, 6yOS 86%) vs HD CDDP (40 mg/m2 x 5) and rest same dose (6yEFS
89.6%, 6yOS 91%(), indicating a better EFS for children at higher doses.
HJ Schmall et al (C Bokemeyer) (JCO 2003;21:4083-91). N=221, poor prognosis Indiana criteria. VIP x 1
�HD VIP + SCAT q 3 wk x 3-4. DLT for CDDP 100 mg/m2 + VP 1750 mg/m2 + IFX 12 g/m2 (mucositis,
CNS, renal and hematological toxicity). M fup 4 y: 5y PFS 68%, 5y DSS 73%.
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C Kollmannsberger et al (Cancer 2006;106:1217-26). Review platrinum refractory testicular GCT. CDDP
refractory shows progression within 4 wks of platinum based chemotherapy. Active drugs: TXL: OR 25%,
GEM OR 145-17%, LOHP OR 13%. Combinations: TXL-GEM OR 21%; GEM + LOHP =R 32-46%; CPT-
CDDP or CTP/LOHP 40-50% OR,(CPT no activity shown in single agent data).
GV Kondagunta et al MSKCC (JCO 2005;27:6549-55). N=46, erecurrence after an initial CR. TIP:TXL 250
mg/m2 civi 24 h d 1 + IFX 1500 mg/m2 x 4d d2-5+ CDDP 25 mg/m2 x 4 d 2-5 + MESNA 500 mg/m2 x 3
after each IFX + DXMTS 20 mg + GCSF 5 ug/kg d 7-18. OR= 32/46 (CR 70%), 2 relapses, 29 continuously
NED. M F up 69 mo, 63% durable responses. 2 yPFS 65%. Patient selection important...
P Bedano et al (LH Einhorn) (JCO 2006;24:5403-7). N=30, recurrent after initial CDDP. EPI 90 mg/m2 d 1 +
CDDP 20 mg/m2 d 1-5 q 3 wk x 4. OR 9 CR (7 NED 25 + to 48+ mo). Active. Acceptable toxicity.
GV Kondagunta et al (JCO 2007;25:85-90). N=48 PD and high risk recurrences. TICE= TXL 200 mg/ m2
civi 24 h + IFX 2 g/m2 x 3 d + Apheresis d 11-13 x 2 cycles, & then CBDCA AUC 21 +VP 400 mg/m2 x 3d
+PBSC x 3 cycles. CR 49% + 6% after surgery (total 26/47. 6 relapses. 24 NED at M F up 40 mo. Prior
experience reported with TICE had CR 56% and NED 50%, quite similar results).
J Hartmann et al (C Bokemeyer) (JCO 2007;25:5742-7). Poor IGCC prognosis group. HDChX. Program
consisted in Standard VIP (1 st cycle without TXL to collect progenitors). VP 1500 mg/m2 + IFX 10 g/m2 +
CDDP 100 mg/m2 (+TXL 135-225 mg/m2, 3 cohorts). Results: 52/53 pts completed 152 cycles. MD
WBC1yCR 52%).
NO differences found. Poor prognostic group AFP half life >7d; BHCG half life >3.5 d had a >1yCR 34%
BEP and 61% HDChX!!.
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GERM CELL TUMORS - SEMINOMA
JA Arranz et al (Germa Lluch JR) (Ann Oncol 2001;12:487-91). N=64, seminoma, stage IIa/b M Fup 34 mo.
CDDP 25 mg/m2 x 4 + VP 100 mg/m2 x 4 q 3 wk. OR 98% (CR 69%), Failure rate 11%, Neutropenia gr 3-4,
32%. 3yTTF 89%; 3yOS 97%.
J Vuky et al MSKCC (JCO 2001;20:297-301). N=27, failure 1 st line therapy. CDDP + IFX. 14 alive DFS
(48%) M F up 72 mo.
P Warde et al (JCO 2002;20:4448-52). N=638, M F up 7 y. Stage I seminoma (pooled data from UK,
Denmark, Canada). 5yRFS 82.3%, with 121 relapses. Factors: size >4cm, invasion rete testis, invasion small
vessels. Multivariate HR 2 & 1.7.
WG Jones et al (JCO 2005;23:1200-8). Stage I seminoma, after orchidectomy. M F up 61 mo. Randomized to
20 Gy/10F/2wk (Relapses 10), vs 30 Gy/15F/3wk (Relapses 11, 0.7% difference. (Toxicity criteria indicated a
difference 20% vs 5%).
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