Dose-dense chemotherapy for untreated poor-prognosis and relapsed germ-cell tumours: an 18-year experience with GAMEC chemotherapy.

OBJECTIVE: To 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 disease and relapse settings. METHODS: This retrospective cohort study was based on 162 patients who received GAMEC dose-dense chemotherapy incorporating actinomycin and high dose methotrexate. Survival outcomes were compared. Risk categorization based on (1) the International Prognostic Factor Study Group (IPFSG) criteria and (2) two factors, lactate dehydrogenase (LDH) levels greater than the upper limit of normal and age ≥35 years, were also compared in terms of survival outcomes using Cox proportional hazard regression modelling. RESULTS: Seventy-five patients with poor-prognosis disease, according to International Germ Cell Cancer Collaborative Group classification, received GAMEC as initial therapy. With a median follow-up of 63 months, the median progression-free survival (PFS) was >14 months. The 2-year PFS rate was 61.5% (95% confidence interval [CI] 49.1-71.6), and the 3-year overall survival (OS) rate was 71.9%. Seventy-six patients received GAMEC as second-line therapy (following failure of bleomycin, etoposide and cisplatin or etoposide cisplatin). The median PFS was 7.5 months (95% CI 5.2-not evaluable), the 2-year PFS rate was 43.5% (95% CI 32.1-54.4) and the 3-year OS rate was 53.7% (95% CI 41.6-64.3). In the third-line setting (n = 11), the 2-year PFS was 18.2% (95% CI 2.8-44.2). Overall, the treatment-related death rate declined from 10.5% in the first 15 years to 2.6% in the last 5 years. CONCLUSION: GAMEC was 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 that based on the updated IPFSG criteria. It is possible to identify patients who are particularly likely to benefit from this treatment, which has the important advantages of short duration and absence of bleomycin, particularly in patients with central nervous system and mediastinal disease. Low-dose induction treatment is associated with safer delivery of treatment without compromising survival.

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy.

OBJECTIVES: CODOX-M/IVAC (cyclophosphamide, vincristine, doxorubicin-methatrexate/ifusamide, etoposide, cytarabine) chemotherapy is commonly used to treat Burkitt lymphoma and in the HIV-negative population. Rituximab is often added with suggested survival benefits. Concerns over increased toxicity in an already immunocompromized population have prevented its routine addition in people living with HIV (PLWH). This study evaluated the effect on treatment-related toxicity and efficacy of adding rituximab to CODOX-M/IVAC chemotherapy in PLWH. DESIGN: Retrospective review of 91 PLWH (74 men) with Burkitt lymphoma treated in five London centers between 2003 and 2013. All patients received combination antiretroviral therapy. RESULTS: Forty-nine patients received CODOX-M/IVAC and 42 rituximab (R)-CODOX-M/R-IVAC. The addition of rituximab did not confer any significant increase in grade 3/4 toxicities including infections, mucositis, diarrhea, renal impairment, and tumor lysis syndrome. There was no significant difference in toxic deaths between groups (P = 0.14). The 2-year overall survival (OS) was greater for patients receiving rituximab {2-year OS 72% [95% confidence interval (CI) 0.22-0.92, hazard ratio 0.46] vs. 55% [95% CI 1.1-4.5, hazard ratio 2.2]; log-rank P = 0.04}. Similarly, the 2-year progression-free survival (PFS) was greater in the rituximab cohort [2-year PFS 81% (95% CI 0.21-0.99, hazard ratio 0.46) vs. 55% (95% CI 1.0-4.8, hazard ratio 2.2); log-rank P = 0.04]. CONCLUSION: Our multicenter analysis is the largest to date in this population and showed that the addition of rituximab to CODOX-M/IVAC chemotherapy confers no increase in toxicity and results in significantly improved OS and PFS in PLWH with Burkitt lymphoma who receive concomitant combination antiretroviral therapy.