CHEMOTHERAPY FOR ADVANCED TESTICULAR GERMCELL TUMORS

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CHEMOTHERAPY FORADVANCED TESTICULAR GERM-CELL
TUMORS

• GOOD-RISK DISEASE
• S. Culine
• CHU Henri Mondor
• Créteil, France

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Objectives

• Definition
• Advanced disease
• Good risk
• Optimal chemotherapy

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Advanced disease

• Definition
• A wrong one !

4
Advanced disease

• Definition
• Abnormal CT scan
• (? IIC in seminoma)
• or
• No normalisation
• of serum tumor markers

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Good risk

• IGCCCG classification
• Absence of non-pulmonary
• visceral metastasis and
• AFP lt 1000 ng/ml and
• hCG lt 5000 IU/ml and
• LDH lt 1.5 N
• IGCCCG, J Clin Oncol, 1997, 15 594

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Prognosis

• IGCCCG classification
• Non seminoma Seminoma
• 56 of cases 90 of cases
• 5-year survival 5-year survival
• 92 86

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Optimal chemotherapy

• The cornerstone trials
• SECSG
• 4 BEP gt 4 PVB
• Equal efficacy, lesser toxicity
• Williams SD, N Engl J Med, 1987, 316 1435

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Optimal chemotherapy

• 1987
• 4 cycles
• Bleomycin 30 mg/w
• Etoposide 100 mg/m2/d d1 to d5
• Cisplatin 20 mg/m2/d d1 to d5
• every 21 days

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Optimal chemotherapy

• The cornerstone trials
• Memorial Sloan Kettering
• 4 EP gt 3 VAB-6
• Equal efficacy, lesser toxicity
• Bosl GJ, J Clin Oncol, 1988, 6 1231

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Optimal chemotherapy

• 1988
• 4 cycles
• Etoposide 100 mg/m2/d d1 to d5
• Cisplatin 20 mg/m2/d d1 to d5
• every 21 days

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Optimizing chemotherapy

• Reducing toxicity
• 4 ? number of cycles
• B90 ? doses (delete ?)
• E500 ? doses (E360)
• P Carboplatin

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Cisplatin or carboplatin ?

• Cisplatin without any doubt ?
• MSKCC
• 4 E500P vs 4 E500C (500 mg/m2)
• N 270 patients (S NS)
• Better DFS with cisplatin
• Bajorin D, J Clin Oncol, 1993, 11 598

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Cisplatin or carboplatin ?

• Cisplatin without any doubt ?
• MRC/EORTC
• 4 B30E360P vs 4 B30E360C (AUC5)
• N 598 patients (NS)
• Better DFS and OS with cisplatin
• Horwich A, J Clin Oncol, 1997, 15 1844

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Cisplatin or carboplatin ?

• Cisplatin without any doubt !
• German group
• 3 B90E500P vs 4 B90E360C (AUC5)
• N 54 patients (NS)
• Higher rate of events with carboplatin
• Bokemeyer A, Ann Oncol, 1996, 7 1015

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Take home messages

• Number 1
• Do not use carboplatin !

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3 or 4 cycles ?

• 3 cycles with B90E500P
• Indiana University
• 4 B90E500P 3 B90E500P
• N 118 patients (SNS)
• Similar DFS and OS
• Saxman SB, J Clin Oncol, 1998, 16 702

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3 or 4 cycles ?

• 3 cycles with B90E500P
• EORTC/MRC
• 3 B90E500P 1 E500P 3 B90E500P
• N 812 patients (SNS)
• Similar 2-year DFS (90.4 vs 89.4)
• de Wit R, J Clin Oncol, 2001, 19 1629

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Take home messages

• Number 2
• 3 cycles of BEP are enough
• when optimal doses of bleomycin
• and etoposide are used

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Can we delete bleomycin ?

• No ! with 3 cycles of E500P
• Indiana University
• 3 B90E500P gt 3 E500P
• N 171 patients (SNS)
• Better DFS and OS with bleomycin
• Loehrer PJ, J Clin Oncol, 1995, 13 470

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Can we delete bleomycin ?

• No ! with 4 cycles of E360P
• EORTC
• 4 B90E360P gt 4 E360P
• N 395 patients (NS)
• Better DFS (95vs 87)
• de Wit, J Clin Oncol, 1997, 15 1837

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Optimal chemotherapy

• 2000
• 3 B90E500P or
• 4 E500P or
• 4 B90E360P
• Is there a role for 4 B30E360P ?

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US BEP

• Results
• 3 B90E500P 4 B30E360P
• Nb patients 83 83
• Responses () 88 87
• GCT deaths 1 9
• p0.008
• Toner GC, Lancet, 2001, 357 739

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Optimal chemotherapy

• Final question
• 3 B90E500P
• or
• 4 E500P ?
• French (GETUG) trial

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GETUG T93BP

• Results
• 3 B90E500P 4 E500P
• NS patients 124 122
• Responses () 95 97
• GCT deaths 5 12
• p0.096
• Culine S, Ann Oncol, 2007, 18 917

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Take home messages

• Number 3
• 3 B90E500P is the gold standard in good-risk
  patients
• (4 E500P in case of contraindication for
  bleomycin)

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Optimal chemotherapy

• Pure seminoma
• Is 4 E500P
• an appropriate option ?

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Pure seminoma

• Probably yes
• MRC
• 4 E500P gt 4 Carboplatin
• N 130 patients
• PFS 84 and OS 89 with EP
• Horwich A, Br J Cancer, 2000, 83 1623

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Optimal chemotherapy

• 2008 Seminoma
• 4 E500P
• or
• 3 B90E500P

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CHEMOTHERAPY FORADVANCED TESTICULAR GERM-CELL
TUMORS

• INTERMEDIATE-RISK
• DISEASE

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Non seminoma

• IGCCCG classification
• Absence of non-pulmonary
• visceral metastasis and
• 1000 lt AFP lt 10,000 ng/ml or
• 5000 lt hCG lt 50,000 UI/ml or
• 1,5 N lt LDH lt 10 N
• IGCCCG, J Clin Oncol, 1997, 15 594

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Seminoma

• IGCCCG classification
• Non pulmonary
• visceral metastasis
• IGCCCG, J Clin Oncol, 1997, 15 594

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Prognosis

• IGCCCG classification
• Non seminoma Seminoma
• 28 of cases 10 of cases
• 5-year survival 5-year survival
• 80 72

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Take home messages

• Number 4
• 4 B90E500P is the gold standard
• in intermediate-risk patients
• Why ? Nothing better !

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Optimal chemotherapy

• 2008
• Limited number of trials
• Mixed with poor-risk patients
• VIP BEP (EORTC)

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Optimal chemotherapy

• 2008 Ongoing trials
• EORTC
• 4 B90E500P versus 4 T B90E500P
• GETUG
• VIP in seminoma