1. Management of recurrent and
refractory germ cell tumors

2. • Good risk GCTs achieve a very good long term
cure approaching 95%
• Poor-risk GCTs require four cycles of BEP that
attains an approximately 45% long-term
disease-free survival
• A significant proportion are either refractory
to the platinum first line chemo regimens,,or
the relapse early

3. Standard guidelines for advanced
disease

4. Management for residual disease

5. What does the NCCN say?

6. Therapy for early relapse and
refractory disease
Salvage regimens…

7. VeIP/VIP

8. Results..
• N : 135
• 49.6 % pts achieved dis. free status after
chemotherapy ( with or without surgery for
residual)
• 32% are alive
• 23.7% are continually free of disease
• All pts had a minimal f/u of 6 yrs from entry
into study

9. Variable No of pts Percentage %
Assessable 56 n/a
Response
CR 20 36
IR 36 64
Status..
Alive disease free 19 34
Alive with disease 4 7
Dead 33 59
Alive, continuously
disease free
13 23

10. • N : 189 ( 1985 to 2012)
• CR: 18.5%
• Marker normalization: 35.4%
• 2yr PFS: 34.3%
• 5yr OS: 42.1%

11. Contribution of gemcitabine…

16. Prognostic factors with salvage chemo

19. Outcomes with second-line salvage therapy for recurrent germ cell tumors.
Sonpavde G et al. The Oncologist 2007;12:51-61
©2007 by AlphaMed Press

20. Role of HDCT and auto BMT?

21. Indiana university experience..

22. • Pts included:
– Those , who received high dose chemotherpay as
salvage and has not progressed within 4 weeks after
the last dose
• Stem cells were harvested with GCSF stimulation
• High dose chemo was given with
– Carboplatin 700mg/m2
– Etoposide 750mg/m2
– On days -5, -4 and -3 of stem cell infusion

26. German data..
• N : 74pts
• ORR : 63% with CR in 31%
• EFS of sensitive disease at 2 yrs: 50%
• Only one pt of 23 who had refractory disease
had 7mo event free survival
• OS at 2 yrs: 44%

27. Other European data..
• N: 150
• Median follow up : 55months
• EFS: 29%
• OS: 29%

28. • N: 80
• 3 # TIP followed by HDCT
• 70% responded to TIP
• 66% responded to HDCT
• 3 yr OS: 30%
• 3 yr EFS: 25%

29. Italian experience.
• N : 84
• Median follow up 46months
• DFS rates:
– Good risk: 69%
– Int. risk: 13%
– Poor risk: 0%

30. High dose chemo: blessing or a
curse??

31. Design..
• 280 pts
• Pts refractory to platinum based chemo were
excluded
four cycles of
cisplatin, ifosfamide
and etoposide (or
vinblastine)
three such cycles
followed by
transplant

34. Roles of surgery??
• N: 125 pts who underwent
postchemotherapeutic resention
• Mean f/u: 120monthns
• 57% long term survivors who had raised TM
• Conslusion: salvage surgery results in long
term survival of more than 50%

35. • N : 16pts
• Six patients (37%) are alive and free of
disease at a mean of seventy-four months
following surgery (range 20 to 145 months).
• Five had RP disease only.
• Ten patients died of disease at a mean of
eight months postoperatively (range 5 to 21
months).

38. • N: 114
• 5 yr OS: 53.9%
• Sixty-one patients (53.5%) are alive with a
medium follow-up of 72 months
• Retroperitoneal pathology revealed
– germ cell cancer in 53.5% of patients,
– teratoma in 34.2% of patients, and
– fibrosis in 12.2% of patients, with
– 5-year survival rates of 31.4%, 77.5%, and 85.7%,
respectively (P < .0001).

39. Surgery after HDCT and auto BMT
• Complete resection in 93% pts
• Pts with viable tumor had poor survival
comapred to teratomas or fibrosis

41. Therapy of late relapses
• Defn: relapses occurring after 2 yrs and in the
absence of a second primary tumor
• Typically chemo refractory
• Different disease biology

42. • N: 83
• Indiana university
• Available specimens
were investigated for
expression of the
transcription regulator
FoxD3 and
apurinic/apyrimidinic
endonuclease and the
presence of
chromosome 12
abnormalities.

43. Results…
• Forty-three of 49 patients who underwent
surgery were rendered disease free (NED), and 20
(46.5%) remain continuously NED
• Thirty-two patients received chemotherapy, but
only six (18.8%) obtained a complete remission.
• Eighteen of these 32 patients were successfully
rendered NED by postchemotherapy surgery, and
12 remain continuously NED.

44. Overall..
• 69 of the 81 treated patients (85.2%) ultimately
achieved an NED state, and
– 38 (46.9%) remain continuously NED with median
follow-up from LR therapy of 24.5 months (range, 1 to
83 months),
– whereas nine other patients are currently NED after
therapy for subsequent relapses
– Conclusion on moleular markers could not be made
i/v/o low no. of samples tested

45. • Follow up of 530pts
• 25 cases of late relapse identified
• Risk was lower with good risk pts

48. Characteristics of relapse..

49. • Median survival 23.9mo
• Median follow up 50.3months
• Only 9 survivors
• CRs were observed with only TIP regimen

50. To summarize..
• Refractory disease and early relapse to be
managed in same lines with salvage chemo +/-
surgery
• HDCT with auto BMT also has shown
promising results
• Later relapse:
– Poor prognosis
– Surgical resection whenever feasible
– Chemo has poor outcomes