Wing M. Ho

Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors.

Hepatitus B virus (HBV) reactivation is a well‐described complication in cancer patients who receive cytotoxic chemotherapy and may result in varying degrees of liver damage. As chemotherapy is used increasingly in cancer patients, HBV reactivation during cytotoxic treatment may become a more common problem. In lymphoma patients, the incidence of chronic HBV infection has been reported to be 26%, of whom 47% developed HBV reactivation during chemotherapy. However, corresponding data for patients with other malignancies undergoing cytotoxic chemotherapy are not known. In this prospective study, hepatitis B surface antigen (HBsAg) was determined in 626 consecutive cancer patients who received cytotoxic chemotherapy over a 12‐month period. Seventy‐eight patients (12%) were found to be HBsAg positive. Thirty‐four (44%) developed raised alanine transaminase during their course of chemotherapy. In these 34 patients, hepatitis was attributed to HBV reactivation in 15 patients (44%), chronic active HBV infection in 1 patient (3%), hepatitis C infection in 1 patient (3%), malignant hepatic infiltration in 2 patients (6%), and the use of hepatotoxic chemotherapeutic agents in 11 patients (32%). The causes of hepatitis were unknown in 4 patients (12%). HBV reactivation was more likely to develop in patients who were male, younger age, HBeAg seropositive, and those with lymphoma. Presence of malignant hepatic infiltration, baseline pre‐treatment alanine transaminase, total bilirubin, and HBV DNA levels did not correlate with the development of HBV reactivation. Of the 15 patients who developed HBV reactivation, antiviral therapy with lamivudine was available and used in 9. There was no HBV‐related mortality during chemotherapy. It is concluded that in patients with chronic HBV infection under chemotherapy, HBV reactivation occurs in nearly 20% of them and accounts for 44% of hepatitis cases. The risk factors identified include male sex, younger age, HBeAg seropositive, and the diagnosis of lymphoma. In HBV endemic areas, patients with risk factors for HBV reactivation should be identified prior to receiving cytotoxic treatment and monitored closely. The potential benefit of lamivudine requires further confirmation. J. Med. Virol. 62:299–307, 2000.

Lamivudine for the Prevention of Hepatitis B Virus Reactivation in Hepatitis B s-Antigen Seropositive Cancer Patients Undergoing Cytotoxic Chemotherapy

PURPOSE For cancer patients receiving cytotoxic chemotherapy, hepatitis B virus (HBV) reactivation is a well described complication resulting in varying degrees of liver damage. The objectives of this study were to assess the efficacy of the antiviral agent lamivudine in reducing the incidence of HBV reactivation and diminishing morbidity and mortality of cancer patients with chronic HBV infection during chemotherapy. PATIENTS AND METHODS Two groups were compared in this nonrandomized study. The prophylactic lamivudine group consisted of 65 patients in a phase II study who were treated with lamivudine before and until 8 weeks after discontinuing chemotherapy. The historical controls consisted of 193 consecutive patients who underwent chemotherapy without prophylactic lamivudine. Significant prognosticators for the development of HBV reactivation were determined based on data from the controls. Potential confounding factors were identified between the two groups. The outcomes were compared. RESULTS In the controls, lymphoma and anthracycline usage were factors identified to be associated with reactivation. The two groups were comparable in most baseline characteristics, although in the prophylactic lamivudine group, there were significantly more patients with lymphoma and receiving anthracyclines. In the prophylactic lamivudine group, there was significantly less HBV reactivation (4.6% v 24.4% in the controls; P <.001), fewer incidences of hepatitis (17.5% v 44.6%; P <.0001) that were less severe (4.8% v 18.7%; P =.0005), and less disruption of chemotherapy (15.4% v 34.6%; P =.0029). The reduction in overall mortality was not statistically different. CONCLUSION Prophylactic lamivudine significantly reduced the incidence of HBV reactivation and the overall morbidity of cancer patients undergoing chemotherapy.

New Utility of an Old Marker: Serial α-Fetoprotein Measurement in Predicting Radiologic Response and Survival of Patients With Hepatocellular Carcinoma Undergoing Systemic Chemotherapy

PURPOSE There are limitations in using radiologic evaluation to assess the treatment outcome of patients with hepatocellular carcinoma (HCC). The use of serial alpha-fetoprotein (AFP) in monitoring response has not been rigorously evaluated. We aimed to study the clinical value of AFP trend in an attempt to validate AFP as a surrogate serologic end point. PATIENTS AND METHODS Participants from a phase III randomized trial of systemic chemotherapy in HCC were studied. Serum AFP was prospectively collected in parallel with clinical and radiologic outcome. AFP response was defined as a decrease in AFP of more than 20% after a minimum of two cycles of chemotherapy. We studied the relationship between AFP response and treatment outcome in terms of radiologic response and overall survival. RESULTS Of 188 patients, 117 patients with elevated serum AFP (> 20 microg/L) and documented radiologic evaluation had received at least two cycles of chemotherapy. A total of 47 AFP responders were identified. AFP responders had better survival than nonresponders (13.5 v 5.6 months, respectively; P < .0001), and AFP response was strongly associated with radiologic response (P < .0001). Multivariate analysis suggested that AFP response was significantly associated with survival (hazard ratio, 0.413; 95% CI, 0.273 to 0.626; P < .0001). AFP responses were frequently observed in patients with radiologically stable disease (SD) and tended to identify a subgroup of SD patients with better survival. CONCLUSION Serial AFP measurement is useful in prognostication and monitoring treatment response in HCC patients undergoing systemic chemotherapy. Incorporation of AFP response into the criteria evaluating treatment outcome should be considered in clinical practice and clinical trials of novel agents in HCC.

Use of lamivudine to prevent hepatitis B virus reactivation during chemotherapy in breast cancer patients

In parts of Asia, about 10% of the population have chronic hepatitis B virus (HBV) infection, and cancer patients who are HBV carriers are frequently complicated by HBV reactivation while receiving cytotoxic chemotherapy. The condition may result in varying degrees of liver damage, causing disruption in chemotherapy and compromising the patients’ prognosis. With the increasing use of chemotherapy paralleling the rise in breast cancer incidence, the occurrence of HBV reactivation is likely to further increase. Recent reports have suggested that the anti-viral agent, lamivudine, may reduce HBV reactivation and its associated morbidity. However, most studies are based on small series of lymphoma patients, while information on the other high risk population, namely breast cancer patients, has been lacking. In this study, we studied the role of lamivudine in preventing HBV reactivation and its associated morbidity in breast cancer patients with chronic HBV infection who were planned for chemotherapy. Two groups were studied. One group consisted of 31 patients who received ‘prophylactic lamivudine’ prior to and until 8 weeks after discontinuing chemotherapy. The other comprised of 61 historical controls who underwent chemotherapy without prophylactic lamivudine. The outcomes, in terms of the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity during chemotherapy were compared. The results revealed that in the prophylactic lamivudine group, despite a significantly higher proportion receiving anthracyclines, there was significantly fewer incidences of hepatitis (12.9 vs. 59.0%, p < 0.001), less HBV reactivation (6.5. vs. 31.1%, p=0.008), and less disruption of chemotherapy (16.1% vs. 45.9%, p=0.006). We conclude that prophylactic lamivudine significantly reduces the incidence of HBV reactivation and the overall morbidity of breast cancer patients undergoing chemotherapy.

Liver resection after irinotecan, 5-fluorouracil, and folinic acid for patients with unresectable colorectal liver metastases : a multicenter phase II study by the Cancer Therapeutic Research Group

The main objectives of this study were to assess the use of irinotecan, 5-fluorouracil (5-FU), and leucovorin (FA) as neoadjuvant chemotherapy for patients with unresectable colorectal liver metastases and to determine the response rate and proportion of patients that could be downstaged to resectable tumors. Forty patients were treated with irinotecan (180 mg/m2 over 30 min) on d 1, FA (200 mg/m2 over 30 min) followed by 5-FU (400 mg/m2 bolus and continuous infusion of 600 mg/m2 over 22 h) on d 1 and 2 every 2 wk. The overall response rate was 55% (95% CI: 39.5–70.4%). The progression-free survival was 12.1 mo (95% CI: 11.4–14.8 mo). The median overall survival was 20 mo (95% CI: 17.7–26.6 mo). Four patients (10%) have undergone liver resection after a median of eight cycles. Those patients remained alive with a median follow up period of 33 mo. The principal grade 3–4 toxicity was neutropenia in 20 patients (50%). We conclude that the regimen of irinotecan/5-FU/FA was highly active in patients with colorectal cancer and liver metastases with limited toxicity. In a subgroup of patients with initial inoperable liver metastases, this regimen was able to downstage the disease to an operable stage.

Hepatitis B viral load predicts survival of HCC patients undergoing systemic chemotherapy

HCC is a common cause of morbidity and mortality. For patients who are not candidates for curative surgery, systemic chemotherapy is one of the standard treatments. In parts of China and the Far East, over 80% of HCC patients have chronic HBV infection. In this study, we aimed to assess the relationship between pre‐chemotherapy HBV viral load and the survival of HCC patients. HBV infection status was determined prior to chemotherapy in 188 patients, 170 of whom had evidence of HBV chronic infection/exposure (160 hepatitis B surface antigen [HBsAg]‐positive, 10 HBsAg‐negative/hepatitis B core antibody–positive). Of these, 125 had pretreatment HBV DNA levels determined via real‐time PCR. Virological data were analyzed using conventional clinical variables to identify factors that influenced survival. Multivariate analysis revealed that high total bilirubin (P = 0.0016; hazard ratio = 1.040 per 1 μM increase; 95% CI 1.015–1.065), HCV infection (P = 0.0095; hazard ratio = 6.955; 95% CI 1.606–30.129), and high HBV DNA level (P = 0.0217; hazard ratio = 1.650; 95% CI 1.076–2.531) affected survival significantly. Exploratory analysis revealed that high levels of pretreatment HBV DNA had a significantly higher incidence of severe hepatitis during chemotherapy. Conclusion: For HCC patients with HBV chronic infection/exposure, a high viral load prior to treatment is an adverse factor for survival and may be associated with a higher incidence of severe hepatitis during chemotherapy. Future strategies to improve the prognosis of HCC patients undergoing chemotherapy should consider supportive therapy that incorporates antiviral therapies to reduce HBV viral load. (HEPATOLOGY 2007;45:1382–1389.)

The evolution of psychological distress trajectories in women diagnosed with advanced breast cancer: a longitudinal study

Anxiety and depression (distress) over the first year following the initial adjuvant therapy for advanced breast cancer (ABC) remain poorly documented in non‐Caucasian populations. This study describes trajectories of distress and their determinants in Chinese women with ABC.

A phase II safety and efficacy study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor pazopanib in patients with metastatic urothelial cancer

BACKGROUND Vascular endothelial growth factor (VEGF) is produced by bladder cancer cell lines in vitro and expressed in human bladder tumor tissues. Pazopanib is a vascular endothelial receptor tyrosine kinase inhibitor with anti-angiogenesis and anti-tumor activity in several preclinical models. A 2-stage phase II study was conducted to assess the activity and toxicity profile of pazopanib in patients with metastatic, urothelial carcinoma. METHODS Patients with one prior systemic therapy for metastatic urothelial carcinoma were eligible. Patients received pazopanib at a dose of 800 mg orally for a 4-week cycle. RESULTS Nineteen patients were enrolled. No grade 4 or 5 events were experienced. Nine patients experienced 11 grade 3 adverse events. Most common toxicities were anemia, thrombocytopenia, leucopenia, and fatigue. For stage I, none of the first 16 evaluable patients were deemed a success (complete response or partial response) by the Response Evaluation Criteria In Solid Tumors criteria during the first four 4-week cycles of treatment. Median progression-free survival was 1.9 months. This met the futility stopping rule of interim analysis, and therefore the trial was recommended to be permanently closed. CONCLUSIONS Pazopanib did not show significant activity in patients with urothelial carcinoma. The role of anti-VEGF therapies in urothelial carcinoma may need further evaluation in rational combination strategies.

Acute toxicity of adjuvant doxorubicin and cyclophosphamide for early breast cancer: a retrospective review of Chinese patients and comparison with an historic Western series

A cohort of 85 Chinese breast cancer patients who received adjuvant chemotherapy with doxorubicin and cyclophosphamide was found to have a significantly higher incidence of grade 3 (n=44, 52%) and grade 4 (n=21, 25%) neutropenia when compared with an historic Western cohort. Also noted was a higher incidence of hepatotoxicity (n=8, 9%). When compared to Caucasian patients, the higher myelotoxicity in our patients may be related to ethnic variation in susceptibility to chemotherapy-related toxicity, lower body mass index with higher percentage of body fat composition, and the popular practice of concurrent alternative medicine during chemotherapy. The higher incidence of hepatoxicity was possibly associated with endemic chronic hepatitis B infection in this geographical area.

Supportive care needs in Hong Kong Chinese women confronting advanced breast cancer

Women with advanced breast cancer (ABC) are living longer, so understanding their needs becomes important. This cross‐sectional study investigated the type and extent of unmet supportive care needs in Hong Kong Chinese women with advanced breast cancer.