TIP salvage chemotherapy
In patients with relapsed testicular seminoma or non-seminomatous germ-cell tumours after cisplatin-based first-line chemotherapy, can paclitaxel, ifosfamide and cisplatin (TIP) achieve durable remission?
Progressive metastatic testicular germ-cell tumours after a complete response to first-line chemotherapy.
TIP is used as conventional-dose second-line chemotherapy; expert germ-cell tumour multidisciplinary review is important.
32/46 patients achieved CR; 29/46 remained continuously disease-free at median follow-up of 69 months (durable CR 63%).
2024 report: 5-year PFS 66% and OS 69% overall; this is a non-randomized cohort, not a comparative trial.
Absolute Effect / reported outcomes
The original phase II study was a selected, single-arm cohort. The long-term report is also non-randomized. There is no valid treatment-versus-control absolute risk reduction, so an NNT is not applicable.
Long-term outcomes in the 104-patient cohort
Favourable response was defined as complete response or partial response with negative tumour markers. Values are source-reported for the full cohort; they are not randomized comparative effects.
Histology subgroup context
| Histology | Favourable response rate | Interpretation |
|---|---|---|
| Seminoma | 89% | Observed in the 2024 long-term cohort; small subgroup, not a powered head-to-head comparison. |
| NSGCT | 75% | Observed in the same cohort; outcomes depend strongly on salvage prognostic factors and resectability of residual disease. |
Regimen and delivery
A commonly used 21-day TIP schedule in the EAU guideline is:
| Drug | Dose | Schedule |
|---|---|---|
| Paclitaxel | 250 mg/m² | 24-hour continuous IV infusion, day 1 |
| Ifosfamide | 1.5 g/m²/day | Days 2–5, with mesna uroprotection |
| Cisplatin | 25 mg/m²/day | Days 2–5 |
Usually planned for four cycles with growth-factor support. An alternative schedule uses paclitaxel 175 mg/m² on day 1, ifosfamide 1.2 g/m²/day and cisplatin 20 mg/m²/day on days 1–5. Use the institution's validated protocol and adjust to organ function and toxicity.
Safety and limitations
TIP is intensive salvage chemotherapy with substantial myelosuppression and risks of febrile neutropenia, infection, transfusion, renal toxicity, neurotoxicity, ototoxicity, electrolyte disturbance, urotoxicity and treatment delays. In the 104-patient cohort, neutropenic fever occurred in 27 patients (reported as 47% in the toxicity-evaluable group); red-cell and platelet transfusions were frequent. Prophylactic G-CSF, mesna, hydration, renal/electrolyte monitoring and specialist supportive care are integral.
Current-practice context · reviewed 18 October 2026
EAU guidance lists four cycles of cisplatin/ifosfamide-based salvage chemotherapy with a third agent—TIP, VIP or potentially GIP—as options after relapse following first-line treatment. No randomized trial has established TIP as superior to high-dose chemotherapy (HDCT) with autologous stem-cell support. Choice should be individualized using relapse risk and discussed at a high-volume germ-cell tumour centre.
The randomized phase III TIGER study (A031102; NCT02375204) compares conventional-dose TIP with high-dose TI-CE as first salvage treatment. Recruitment has ended, but results were not posted on the registry sources reviewed; check the live registry for updates.