Oxaliplatin and capecitabine (Xelox) in association with highly active antiretroviral therapy in advanced hepatocarcinoma HIV/HCV-infected patients
2006; Elsevier BV; Volume: 17; Issue: 7 Linguagem: Inglês
10.1093/annonc/mdj140
ISSN1569-8041
AutoresMassimiliano Berretta, Arben Lleshi, Fabrizio Di Benedetto, Alessandra Bearz, Michele Spina, Umberto Tirelli,
Tópico(s)Colorectal Cancer Treatments and Studies
ResumoThe introduction of highly active antiretroviral therapy (HAART) had a dramatic impact on the morbidity and mortality of human immunodeficiency virus (HIV)-infected patients with a decline in the incidence of several opportunistic infections, as well as of acquired immunodeficiency syndrome (AIDS)-defining malignancies [1.Bonnet F. Lewden C. May T. et al.Malignancy-related causes of death in human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy.Cancer. 2004; 101: 317-324Crossref PubMed Scopus (215) Google Scholar]. On the other hand, due to the prolonged expectancy of life and the ageing of the HIV-positive population, tumours are now the major cause of death [1.Bonnet F. Lewden C. May T. et al.Malignancy-related causes of death in human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy.Cancer. 2004; 101: 317-324Crossref PubMed Scopus (215) Google Scholar], and among them hepatocellular carcinoma (HCC) has become an increasing cause of mortality in these patients, especially in those HCV/HBV co-infected [2.Puoti M. Bruno R. Soriano V. et al.Hepatocellular carcinoma in HIV-infected patients: epidemiological features.clinical presentation and outcome. AIDS. 2004; 18: 2285-2293Google Scholar].Oxaliplatin and capecitabine are antineoplastic agents currently indicated for the treatment of gastrointestinal malignancies. The combination of oxaliplatin and capacitabine (Xelox) has been used in gastrointestinal tumours. Recently oxaliplatin and capecitabine have been used, separately, in the treatment of advanced HCC [3.Cerosimo R.J. Oxaliplatin-associated neuropathy: a review.Ann Pharmacother. 2005; 39: 128-135Crossref PubMed Scopus (194) Google Scholar, 4.Patt Y.Z. Hassan M.M. Aguayo A. et al.Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma.and gallbladder carcinoma. Cancer. 2003; 101: 578-586Google Scholar]. In the literature there is no report on the use of Xelox in the treatment of HCC neither in the general nor in HIV-infected population. Therefore the feasibility and efficacy of Xelox alone or in combination with HAART are still unknown in patients with HIV- (and HCV-co-) infection and HCC.Four consecutive patients with HIV/HCV-co-infection and advanced HCC have been treated at the National Cancer Institute of Aviano (Italy), from March 2004 to September 2005 with the Xelox-regimen (oxaliplatin 130 mg/m2 intravenously, day 1 and capecitabine 1000 mg/m2 orally twice-a-day, days 1–14, both prescribed on a 21-day cycle) [5.Jatoi A. Murphy B.R. Foster N.R. et al.Oxaliplatin and capecitabine in patients with metastatic adenocarcinoma of the esophagus, gastroensophageal junction and gastric cardia: a phase II study from the North Central Cancer Treatment Group.Ann Oncol. 2006; 17: 29-34Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar] and concomitant HAART.Before treatment, patients have been staged by means of physical examinations, complete blood cell count (including CD4 and CD8 T-cell count), blood chemistry, HIV, and HCV or HBV viral load, alfaphetoprotein (AFP), computed tomography of thorax, abdomen, and pelvis and ECG.The diagnosis of HCC has been made through ultrasonography and Computed Scan Tomography with contrast enhancement.HAART has been given concomitantly since the beginning of chemotherapy, regardless of CD4 T-cell count and HIV viral load, and it has been selected on the basis of patients' prior antiretroviral exposure.After every chemotherapy cycle, filgrastim (300 mg/d SC, from day 5 to complete haematological recovery) has been administered as a prophylactic measure.Characteristics of patients, response to Xelox, and toxicities are shown in Table 1.Table 1Patient characteristicsSex Male3 Female1 Age median (range)45 (40–47)Risk factor for HIV infection IVDUaIntravenous drug use.4 Median CD4 (μl)338 Median HIV viral load<50HIV stage A1→A33 B1→B31 C1→C30Child-Pugh class A0 B2 C2 Hepatitis C virus antibody positive4Performance status 0–11 ≥23Number of liver nodules Single nodule0 Multiple nodules or infiltrating4Alphafetoprotein ng/dl 4003 Portal vein invasion3 Extra hepatic metastases3 Total number of cycles of chemotherapybXelox regimen [5].11Response the chemotherapy Complete remission0 Partial remission1 Stable disease0 Progression disease3Haematological toxicities G1–G21 G3–G43Gastrointestinal toxicities G1–G22 G3–G40Peripheral neuropathy G1–G22 G3–G40a Intravenous drug use.b Xelox regimen [5.Jatoi A. Murphy B.R. Foster N.R. et al.Oxaliplatin and capecitabine in patients with metastatic adenocarcinoma of the esophagus, gastroensophageal junction and gastric cardia: a phase II study from the North Central Cancer Treatment Group.Ann Oncol. 2006; 17: 29-34Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar]. Open table in a new tab Even if the recycling has not been performed at the scheduled time in all patients due to haematological toxicity, no patient has been hospitalised because of severe toxicity or opportunistic infection.There has been no apparent interaction between Xelox and concomitant HAART administration. Partial remission and disease progression have been observed in 1 and 3 patients, respectively. Up to now the patient in partial remission is still alive after 4 months while the other three patients died for progression of the disease.In conclusion, these data demonstrate that Xelox regimen with concomitant HAART is feasible and the HIV infection is not a limiting factor for its use. Moreover, the concomitant use of HAART does not seem to increase the toxicity of this regimen, although it is too early to evaluate the Xelox activity in these particular setting of patients. The introduction of highly active antiretroviral therapy (HAART) had a dramatic impact on the morbidity and mortality of human immunodeficiency virus (HIV)-infected patients with a decline in the incidence of several opportunistic infections, as well as of acquired immunodeficiency syndrome (AIDS)-defining malignancies [1.Bonnet F. Lewden C. May T. et al.Malignancy-related causes of death in human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy.Cancer. 2004; 101: 317-324Crossref PubMed Scopus (215) Google Scholar]. On the other hand, due to the prolonged expectancy of life and the ageing of the HIV-positive population, tumours are now the major cause of death [1.Bonnet F. Lewden C. May T. et al.Malignancy-related causes of death in human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy.Cancer. 2004; 101: 317-324Crossref PubMed Scopus (215) Google Scholar], and among them hepatocellular carcinoma (HCC) has become an increasing cause of mortality in these patients, especially in those HCV/HBV co-infected [2.Puoti M. Bruno R. Soriano V. et al.Hepatocellular carcinoma in HIV-infected patients: epidemiological features.clinical presentation and outcome. AIDS. 2004; 18: 2285-2293Google Scholar]. Oxaliplatin and capecitabine are antineoplastic agents currently indicated for the treatment of gastrointestinal malignancies. The combination of oxaliplatin and capacitabine (Xelox) has been used in gastrointestinal tumours. Recently oxaliplatin and capecitabine have been used, separately, in the treatment of advanced HCC [3.Cerosimo R.J. Oxaliplatin-associated neuropathy: a review.Ann Pharmacother. 2005; 39: 128-135Crossref PubMed Scopus (194) Google Scholar, 4.Patt Y.Z. Hassan M.M. Aguayo A. et al.Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma.and gallbladder carcinoma. Cancer. 2003; 101: 578-586Google Scholar]. In the literature there is no report on the use of Xelox in the treatment of HCC neither in the general nor in HIV-infected population. Therefore the feasibility and efficacy of Xelox alone or in combination with HAART are still unknown in patients with HIV- (and HCV-co-) infection and HCC. Four consecutive patients with HIV/HCV-co-infection and advanced HCC have been treated at the National Cancer Institute of Aviano (Italy), from March 2004 to September 2005 with the Xelox-regimen (oxaliplatin 130 mg/m2 intravenously, day 1 and capecitabine 1000 mg/m2 orally twice-a-day, days 1–14, both prescribed on a 21-day cycle) [5.Jatoi A. Murphy B.R. Foster N.R. et al.Oxaliplatin and capecitabine in patients with metastatic adenocarcinoma of the esophagus, gastroensophageal junction and gastric cardia: a phase II study from the North Central Cancer Treatment Group.Ann Oncol. 2006; 17: 29-34Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar] and concomitant HAART. Before treatment, patients have been staged by means of physical examinations, complete blood cell count (including CD4 and CD8 T-cell count), blood chemistry, HIV, and HCV or HBV viral load, alfaphetoprotein (AFP), computed tomography of thorax, abdomen, and pelvis and ECG. The diagnosis of HCC has been made through ultrasonography and Computed Scan Tomography with contrast enhancement. HAART has been given concomitantly since the beginning of chemotherapy, regardless of CD4 T-cell count and HIV viral load, and it has been selected on the basis of patients' prior antiretroviral exposure. After every chemotherapy cycle, filgrastim (300 mg/d SC, from day 5 to complete haematological recovery) has been administered as a prophylactic measure. Characteristics of patients, response to Xelox, and toxicities are shown in Table 1. Even if the recycling has not been performed at the scheduled time in all patients due to haematological toxicity, no patient has been hospitalised because of severe toxicity or opportunistic infection. There has been no apparent interaction between Xelox and concomitant HAART administration. Partial remission and disease progression have been observed in 1 and 3 patients, respectively. Up to now the patient in partial remission is still alive after 4 months while the other three patients died for progression of the disease. In conclusion, these data demonstrate that Xelox regimen with concomitant HAART is feasible and the HIV infection is not a limiting factor for its use. Moreover, the concomitant use of HAART does not seem to increase the toxicity of this regimen, although it is too early to evaluate the Xelox activity in these particular setting of patients.
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