Effects Of Different Chemotherapy Regimens Research Articles

Chemotherapy-Associated Liver Injury in Patients with Colorectal Liver Metastases: A Systematic Review and Meta-analysis

BackgroundChemotherapy-associated liver injury is a major cause for concern when treating patients with colorectal liver metastases. The aim of this review was to determine the pathological effect of specific chemotherapy regimens on the hepatic parenchyma as well as on surgical morbidity, mortality and overall survival.MethodsA systematic review of the published literature and a meta-analysis were performed. For each of the variables under consideration, the effects of different chemotherapy regimens were determined by calculation of relative risks by a random-effects model.ResultsHepatic parenchymal injury is regimen specific, with oxaliplatin-based regimens being associated with grade 2 or greater sinusoidal injury (number needed to harm 8; 95 % confidence interval [CI] 6.4–13.6), whereas irinotecan-based regimens associated with steatohepatitis (number needed to harm 12; 95 % CI 7.8–26). The use of bevacizumab alongside FOLFOX reduces the risk of grade 2 or greater sinusoidal injury (relative risk 0.34; 95 % CI 0.15–0.75).ConclusionsChemotherapy before resection of colorectal liver metastases is associated with an increased risk of regimen-specific liver injury. This liver injury may have implications for the functional reserve of the liver for patients undergoing major hepatectomy for colorectal liver metastases.

The Role of the Rituximab Partner Chemotherapy Regimen In Young Patients with Good-Prognosis Diffuse Large B-Cell Lymphoma (DLBCL): Results of the 6-Year Follow-up of the Mint Study of the Mabthera International Trial (MInT) Group.

AbstractAbstract 2826 Background:The addition of rituximab to CHOP-21 significantly improved clinical outcome in elderly patients with DLBCL (Coiffier et al., 2002). In young patients, the MInT trial, where young good-prognosis patients were randomized to receive a CHOP-like regimen or the same CHOP-like regimen plus rituximab, had to be stopped early because of superiority of the rituximab arm, and results were published with a median follow-up of 34 months (Pfreundschuh et al., Lancet Oncology 2006;379–91). Objective:Because the MInT study was the first study to show a survival benefit of the addition of rituximab to a CHOP-like regimen in young good-prognosis patients, it is important to analyze the effect of different chemotherapy regimens on long-term outcome. Methods:In a phase III intergroup study with participating cooperative groups from 18 countries, previously untreated young (18-60 years) patients with good-prognosis DLBCL (age-adjusted IPI 0 or 1, stages II-IV and stage I with bulky disease) were randomized to receive 6 cycles of a CHOP-like regimen (CHEMO) or the same chemotherapy plus rituximab 375 mg/m2, given on day 1 of each 3-weekly regimen and on days 1, 22, 43, 64, 85 and 106 of the 2-week regimens, respectively (R-CHEMO). Radiotherapy (30-40 Gy) was planned to sites of initial bulky disease and/or extranodal involvement. The primary endpoint was event-free survival (EFS) with events defined as failure to achieve complete remission, progressive disease, relapse, death or additional (unplanned) therapy. Results:Between 05/2000 and 10/2003 a total of 823 patients were recruited of whom 396 were allocated to receive CHOP-21, 361 to CHOEP-21, 34 to MACOP-B, and 32 to PMitCEBO with or without rituximab. Patients'characteristics were not different between the treatment arms with the exception that patients in the MACOP-B and R-MACOP-B arm had a more favorable prognostic profile. Toxicity, incidence of adverse events and severe adverse events in the different CHEMO and the R-CHEMO arms were not significantly different. After a median observation time of 70 (0.03-117) months, the 6-year EFS rates of patients assigned to CHEMO only were 50.4%, 60%, 41.7%, and 78.6% for CHOP-21, CHOEP-21, PMitCEBO, and MACOP-B, respectively. In an adjusted multivariate Cox regression model for EFS restricted to CHEMO patients, only the CHOEP-21 hazard ratio (HR) was significant (HR=0.73; p=0.05) compared to CHOP-21, while the hazard ratios of the different chemotherapies were not significantly different for PFS and OS (6 year PFS-rates: 60.2%, 64.8%, 67.5%, 86.2%; and 6 year OS-rates: 78.8%, 80.2%, 65.5%, and 100.0%, respectively). In patients assigned to R-CHEMO, 6-year EFS rates were 74.9%, 75%, 36.5%, and 86.7% for CHOP-21, CHOEP-21, PMitCEBO and MACOP-B, respectively. Likewise, PMitCEBO patients tended to have lower PFS (6-year rates: 79.1%, 81.9%, 58.9, and 86.7%, respectively) and OS (6-year rates: 91.9%, 89.4%, 80.0 and 94.1%, respectively). The poor outcome after R-PMitCEBO in contrast to R-CHOP was confirmed by multivariable Cox regression restricted to R-CHEMO and adjusting for aaIPI and bulky disease. Hazard ratio of PMitCEBO was significant for EFS (HR 4.35, p<0.001) and PFS (HR 3.62, p=0.002), with a strong trend for OS (HR 3.11, p=0.073). Conclusion:While the addition of rituximab to CHOP-like regimens usually results in reduced differences between chemotherapy regimens (“chemo-equalizer” effect, e.g. disappearance of the superiority of CHOEP over CHOP after the addition of rituximab), combination of rituximab with some regimens might result in an unexpectedly poor outcome. Therefore, rituximab should not be combined with regimens other than CHOP outside randomized trials. Supported by Roche, Deutsche Krebshilfe and KML. Disclosures:Jäger:Roche: Honoraria, Research Funding. Pettengell:Roche: Honoraria. Pfreundschuh:Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.

Development and evaluation of a decision aid for patients considering first‐line chemotherapy for metastatic breast cancer

Treatment decisions in advanced breast cancer are complex, with enhanced quality of life and survival among important treatment goals. Patients with metastatic breast cancer face the decision of whether or not to have chemotherapy, and many wish to be involved in this decision. We report the development and evaluation of a decision aid (DA) designed to assist patients facing this treatment decision. Women with metastatic breast cancer (n = 17)and medical oncologists in Australia and Canada (n = 7) were invited to evaluate the DA. A DA was developed for patients with hormone resistant metastatic breast cancer considering chemotherapy. The DA presented options of supportive care, with or without chemotherapy. Potential benefits and side effects of different chemotherapy regimens, and evidence-based prognostic estimates were described,and a values clarification exercise included. Patient questionnaires evaluating information and decision involvement preferences, attitudes toward the DA and oncologist feedback regarding attitudes toward the DA. Seventeen patients participated; fifteen desired as much information about their illness as possible; sixteen wished to be actively involved in the decision-making process. The majority rated the DA as highly acceptable, clear and informative, and would recommend it to others facing this treatment decision. This is the first DA for patients with advanced metastatic breast cancer considering chemotherapy. A randomized trial is underway to evaluate its role in clinical decision-making.

Effects of different chemotherapy regimens and tamoxifen for HER2 over-expressed breast cancer adjuvant therapy

11048 Background: To evaluate effects of different adjuvant chemotherapy regimens and TAM in HER-2-overexpressed breast cancer patients. Methods: To study 1625 primary breast cancer cases after operation from 2002.7 to 2005.11 given adjuvant chemotherapy ,600 cases given CMF, 600 cases given CEF, and 425 cases given T-regimen (anthracyclines follow taxanes),1090 HR+ cases given tamoxifen. HER-2 expression were measured by immunohistochemistry (IHC). Median follow-up time is 42 months. Results: (1)3yr DFS of HER-2 over-expression is inferior to HER-2 negative ones in CMF group(p&lt;0.05), no difference between HER-2- overexpressed and HER-2-negative group treated with either CEF or taxanes-based regimen (p&gt;0.05). Subgroup analysis suggested: patients treated with CMF, 3yr DFS of HER-2 over-expression is inferior to HER-2-negative ones in node-positive subgroup, but no difference in node-negative ones; HER-2 expression has no influence on effects of CEF or T-regimen in node-positive or node-negative subgroup. (2) 425 HER-2 over-expressed patients(183 cases given CMF , 121 cases given CEF , and 121 cases given T-regimen): compared to CMF, anthracyclines and taxanes are more effective, but no difference between anthracyclines and T-regimen. (3) 235 patients with HER-2 over- expression and node-postive (72 cases given CMF , 68 cases given CEF, and 95 cases given T-regimen):, anthracyclines and taxanes are more effective than CMF, but no difference between anthracyclines and T-regimen. (4)3yr DFS is 91.23% in HER-2 over-expressed group and 93.42% in HER-2-negative group (p=0.04) with TAM. HER-2 over-expressed patients are resistant to TAM. (5) Subgroup analysis suggested that: 3yr DFS is 88.67% with HER-2 over-expression and 92.20% with HER-2-negative in postmenopausal node-positive subgroup(p=0.0069), postmenopausal patients with HER-2 over-expression and node-positve are resistant to TAM; no difference in either premenopausal or postmenopausal node-negative subgroup (p&gt;0.05). Conclusions: No difference between Anthracyclines based and T-regimens for HER2 over-expressed patients with node-positive for 3yr DFS.Postmenopausal ER+/PR+ patients with HER2 over- expression are resistant to Tamoxifen endocrine therapy. No significant financial relationships to disclose.

Lifestyle factors and survival in women with breast cancer.

With increasing longevity and more effective cancer therapies, the population of cancer survivors is increasing. For example, it is estimated that there are over 2 million breast cancer survivors in the United States. Among cancer survivors and their families, there is substantial interest in whether there is anything that they can do beyond conventional therapy to improve their prognosis. Chief among these is interest in diet and use of complementary and alternative therapies. Despite this interest, there is surprisingly little that is known about the effects of these factors on cancer survival. This is in part because of the usual approach to research on diet and breast cancer in human populations. Studies that have had food and nutrition as a main interest have focused almost exclusively on cancer etiology and prevention; there are literally hundreds of such studies. Meanwhile, studies of populations after a breast cancer diagnosis have rarely considered lifestyle factors. Such studies have focused largely on therapeutics, such as effects of different chemotherapy regimens, or prognostic factors, such as the effects of stage of disease, hormone receptor status, or gene expression signatures on prognosis. To the extent that lifestyle factors have been a focus of cancer prognosis studies, they have often been aimed at the question of whether they impact quality of life, and not on whether they influence cancer survival or recurrence. There have been a handful of studies that have had lifestyle factors such as diet and physical activity as a principal focus. In addition to 2 randomized trials, the Women's Intervention Nutrition Study (WINS) and the Women's Healthy Eating and Living Study, there are at least 5 ongoing prospective cohort studies in breast cancer survivors that have diet as a main focus. Although these studies differ in various aspects, they are all aimed at examining whether differences in diet may result in differences in recurrence and mortality rates. One such study, the Pathways Study, is a prospective cohort study that began recruitment of study participants in early 2006. This study is unique in that it is enrolling women as soon after breast cancer diagnosis as is practical, whereas other studies have generally enrolled women after completion of adjuvant therapy or later. This and other studies promise to provide some of the first objective information regarding diet and breast cancer prognosis and serve as models for studies of diet and prognosis of other cancers.

P-477: Histological quantification of the impact of chemotherapy on human primordial follicle reserve in women

Various chemotherapy agents, especially of the alkylating category, have been associated with premature ovarian failure. Animal studies have shown the direct impact of these agents on primordial follicle (PF) reserve but there is no quantitative evidence of chemotherapy-induced PF loss in humans. Our aim was to quantify the impact of chemotherapy on PF density in human ovarian cortical pieces. Prospective quantitative histological study with controls. Of 17 cancer patients undergoing ovarian freezing for fertility preservation, 8 had received prior chemo and/or radiotherapy (CRT group) and 9 did not (control group). Prior to cryopreservation, a 5x5 mm cortical piece was immediately fixed, paraffin embedded, and serially sectioned. PF density was determined as the mean of follicle counts/mm2 in every fifth section. Patient distribution based on the cancer diagnosis is shown in table 1. Mean ages of CRT and controls were similar (27.5 ± 2.7 vs. 27.7 ± 2.4, p>0.05). However, the mean PF density was significantly lower in the CRT group compared to controls (5.78 ± 1.5 vs. 9.31 ± 2.6, p<0.05). The effect of different chemotherapy regimens and radiotherapy on ovarian reserve in comparison to age-matched controls is illustrated in figure-1. In an 18 year-old acute myelogenous leukemia (AML) patient who had received two courses of a non- alkylating regimen (ADE-GMTZ: cytarabine, daunorubicin, etoposide, gemtuzumab) baseline PF density was comparable to an age-matched patient with Hodgkin lymphoma (HL), who had not received chemotherapy before ovarian freezing (14.4 ± 1.6 vs. 15.3 ± 1.8, p>0.05). In a 22-year-old patient who had received one course of CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) for HL, baseline PF density was significantly lower than the density of an age-matched patient with the same disease who did not receive chemotherapy (6.17 ± 0.7 vs.16.5 ± 3.5, p<0.001). In another patient at age 33 who received 7 courses of CHOP before ovarian freezing, baseline PF density was significantly lower than two age-matched control patients (1.5 ± 0.65 vs. 5.23 ± 1.1, p<0.01 and 1.5 ± 0.65 vs. 5.66 ± 0,9, p<0.01) with breast cancer. Of the two patients at age 24, the baseline PF density of the patient with HL who received a non-alkylating regimen (6 courses of ABVD: Adriamycin, Bleomycin, Vinblastin, Dacarbazine) was significantly higher than a patient of the same age with synovial carcinoma who had received an alkylating regimen (VACAR: vincristine, cyclophosphamide, dactinomycin and doxorubicin) plus inguinal radiotherapy (600cGy) (7 ± 1.7 vs. 4.52 ± 0.89, p<0.05). Of the 30 year-old two patients, one had ovarian tissue removed before chemotherapy for breast cancer and had a significantly higher PF density compared to the other patient who had been treated with pelvic radiotherapy for cervical carcinoma (8.6 ± 1.9 vs. 4.64 ± 0.8, p<0.05). This is the first study to demonstrate the impact of chemotherapy on primordial follicles by histological evaluation from human tissue. Based on these histological data alkylating agents appear to have a significant negative impact on ovarian reserve.Tabled 1

Impact of chemotherapy regimens prior to endocrine therapy

The 33-month median follow-up of the ATAC (anastrozole and tamoxifen, alone or in combination) trial showed a potential interaction between anastrozole and previous chemotherapy; however, this was much smaller at 47 months' median follow-up. When the effects of different chemotherapy regimens were evaluated at that time, the apparent interaction was limited to patients who had received cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). In this retrospective analysis of 68-month data, we investigated the impact of prior chemotherapy, including different chemotherapy regimens, on time to recurrence. The chemotherapy regimens were 1) CMF only; 2) anthracycline-containing regimens (anthracycline or anthracycline and CMF); and 3) other chemotherapy regimens, including taxane-containing combinations. No evidence was found for an interaction between prior chemotherapy and anastrozole (hazard ratio [HR] 0.89 vs. 0.74 for those with or without prior chemotherapy, respectively; P = .21 for interaction). For those with prior chemotherapy, the HR of anastrozole when compared with that of tamoxifen shifted from 0.98 (95% confidence intervals [CI], 0.76-1.28) at 47 months' median follow-up to 0.89 (95% CI, 0.71-1.12) at 68 months' median follow-up and was closer to the overall treatment effect (HR, 0.79; 95% CI, 0.70-0.90). No differences according to type of chemotherapy were seen, and a benefit for anastrozole was also now apparent for patients receiving prior CMF (HR, 0.89; 95% CI, 0.63-1.24). On the basis of the 5-year Completed Treatment Analysis, the ATAC trial does not indicate that the relative treatment benefits of anastrozole differ significantly between patients who received prior chemotherapy and those who did not.

Impact of adjuvant chemotherapy prior to endocrine therapy: 68 month results from the ‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial

608 Background: Previous analyses of the ATAC trial demonstrated initial adjuvant treatment with anastrozole (A) has significant efficacy and tolerability advantages over tamoxifen (T). At 33 months’ median follow-up there was a potential interaction with previous chemotherapy, which was less apparent at 47 months’ median follow-up. When the effects of different chemotherapy regimens were retrospectively evaluated at 47 months, the apparent interaction was limited to patients who had received cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Here we evaluate the results from the ATAC trial at 68 months’ median follow-up to assess the effect of different chemotherapy regimens on time to recurrence (TTR) over the full 5-year treatment period. Methods: Chemotherapy regimens were (1) CMF, (2) anthracycline (AC)-containing regimens (AC, cyclophosphamide ± 5-fluorouracil), (3) other chemotherapies, including taxane-containing combinations. The impact of regimens on TTR was calculated and expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Consistent with the 47-month analysis, superiority for TTR was maintained for A versus T in the AC-containing and taxane-containing subgroups. Advantages for A are now evident with CMF. Adjusting for chemotherapy type had only a minimal effect on TTR. Conclusions: Despite the previously reported interaction within the CMF-group, additional follow-up has confirmed that the benefits of A over T are maintained regardless of the type of chemotherapy given. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca

Effect of different chemotherapy regimens on peripheral-blood stem-cell collections in patients with breast cancer receiving granulocyte colony-stimulating factor.

To evaluate the effects of chemotherapy regimens on peripheral-blood stem-cell (PBSC) yields in patients with breast cancer who receive granulocyte colony-stimulating factor (G-CSF). One hundred patients with breast cancer received cyclophosphamide 4 g/m2 for dose (CY) (n = 10), CY and etoposide 600 mg/m2 (CE) (n = 13), CE and cisplatin 105 mg/m2 (CEP) (n = 19), or CY and paclitaxel 170 mg/m2 (n = 58), followed by G-CSF. PBSC collections were initiated when the WBC count recovered to greater than 1 x 10(9)/L. A multivariate analysis was undertaken to evaluate the effects of different chemotherapy regimens and patient variables on PBSC collections as measured by the yield of CD34+ cells. The medians of average daily CD34+ cell yields for patients who received paclitaxel plus CY, CE, and CEP with G-CSF were 12.9, 11.03, and 5.37 x 10(6)/kg, respectively, compared with 2.02 x 10(6)/kg in the reference group that received CY with G-CSF (P = < .0001, .002, and .09, respectively). On first-day collections, patients who received paclitaxel plus CY, CE, and CEP with G-CSF yielded medians of 11.07, 8.09, and 3.52 x 10(6) CD34+ cells/kg, respectively, compared with 0.90 x 10(6)/kg in the reference group that received CY with G-CSF (P = .0006, .02, and .09, respectively). The number of previous cycles of chemotherapy, previous radiotherapy, marrow involvement, and phase and stage of disease did not have statistically significant effects on CD34+ cell yield. Combination chemotherapy regimens were superior to single-agent CY for the mobilization of CD34+ cells.