Shamash, J; Mee, M; Sarker, S-J; Wilson, P; Ansell, W; Greenwood, M; Berney, D; Shamash, J; Mee, M; Sarker, S-J; Wilson, P; Ansell, W; Greenwood, M; Berney, D; Alifrangis, C; - view fewer (2020) Dose dense chemotherapy for untreated poor prognosis and relapsed germ cell tumours - An 18 year experience with GAMEC chemotherapy. BJU International , 125 (6) pp. 843-852. 10.1111/bju.14947.

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Abstract

Background: The role of dose intensified cisplatin‐based regimens as alternatives to conventional Bleomycin, etoposide and cisplatin (BEP) based treatments in untreated poor risk testicular cancer, and their utility in recurrence following first line chemotherapy remains unresolved. Here we report a single Centre experience of the regimen GAMEC (granulocyte colony stimulating factor, actinomycin‐D, methotrexate with folinic acid rescue, etoposide and cisplatin) over 18 years in both untreated and relapse settings. / Methods: This retrospective cohort study is based on 162 patients who received the GAMEC–both dose dense chemotherapy and incorporation of actinomycin and methotrexate. Survival outcomes were compared and risk categorisation methods of the IPFSG and also based on LDH>ULN and Age>=35 were compared in terms of survival outcomes using Cox proportional hazard regression modelling. / Results: Seventy five patients with IGCCCG poor prognosis disease received GAMEC as initial therapy. With a median follow‐up of 63 months, median PFS was >14 months. Two‐year progression free survival (PFS) rate was 61.5% (95% CI: 49.1‐71.6) and the 3‐yr overall survival (OS) was 71.9%. Seventy six received GAMEC as second line (following failure of BEP or EP). The median PFS was 7.5 months (95% CI: 5.2‐NE), the 2‐yr PFS rate was 43.5% (95% CI: 32.1‐54.4) and the 3‐yr OS was 53.7% (41.6‐64.3). In the 3rd line setting (n=11) the 2y PFS was 18.2% (95%CI: 2.8‐44.2). Overall, the TRD rate declined from 10.5 % in the first 15 years to 2.6% in the last 5 years. / Conclusion: GAMEC is an effective regimen in untreated poor prognosis disease and on relapse following conventional cisplatin and etoposide based chemotherapy. Risk categorization based on LDH/Age is more sensitive than IPFSG2 criteria. It is possible to identify patients particularly likely to benefit from this treatment whose short duration and absence of bleomycin are significant advantages, particularly in patients with central nervous system and mediastinal disease. Low dose induction treatment is associated with safer delivery of treatment without compromising survival.

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