[show abstract][hide abstract] ABSTRACT: Interleukin-1 (IL-1) beta is a putative mediator of the cancer anorexia/weight loss syndrome, and certain polymorphisms of its gene are thought to be associated with a greater risk of gastric cancer. Do these IL-1 beta genetic polymorphisms predispose patients with gastric and gastroesophageal cancer to the anorexia/weight loss syndrome? This study focused on 44 patients with metastatic gastric and gastroesophageal cancer. All underwent genotyping, completed serial quality-of-life questionnaires germane to appetite, and underwent meticulous serial follow-up. Patients with the IL-1 beta-31 C/T and T/T genotypes were more likely to describe a worse appetite at baseline than were those with the C/C genotype. In addition, patients with the IL-1 beta+3954 C/T and T/T genotypes showed greater improvements in their weight (P = 0.02) and in survival (hazard ratio, 0.3; P = 0.04) over time than did patients with the C/C genotype. These associations occurred independently of tumor response. These preliminary data suggest that certain interleukin-1 beta genetic polymorphisms may modulate the cancer anorexia/weight loss syndrome in patients with metastatic gastric and esophageal cancer. Confirmatory studies are warranted.
The journal of supportive oncology 02/2007; 5(1):41-6.
[show abstract][hide abstract] ABSTRACT: This clinical trial evaluated the addition of fluoxymesterone (Flu) to tamoxifen (Tam) in women with resected early stage breast cancer and attempted to corroborate the findings of superiority for the combination over Tam alone seen in a previous randomized trial in metastatic disease.
Postmenopausal women with early stage breast cancer that was known to be estrogen receptor (ER) positive were randomized to treatment with Tam (20 mg per day orally for 5 years) alone or combined with Flu (10 mg orally twice per day for 1 year). The primary endpoint was relapse-free survival (RFS) defined as local-regional or distant recurrence including ductal carcinoma in situ of the ipsilateral, but not contralateral breast, and death from any cause.
There were 541 eligible patients entered between 1991 and 1995 and the treatment arms were balanced with respect to patient characteristics. The median follow up of patients still alive was 11.4 years. No significant difference was found between Tam plus Flu and Tam alone in terms of RFS or overall survival. The adjusted hazard ratio (Tam+Flu/Tam) for relapse or death without relapse was estimated to be 0.84 (95% CI: 0.64-1.10) and that for death was 0.89 (95% CI: 0.67-1.18). As expected there was more virilization in women who received Flu.
This clinical trial did not demonstrate superiority of Tam plus Flu over Tam alone as adjuvant therapy for postmenopausal women with resected early breast cancer known to be ER positive.
Breast Cancer Research and Treatment 08/2006; 98(2):217-22. · 4.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: A pooled analysis was performed to examine the impact of pretreatment factors on overall survival (OS) and time to progression (TTP) in patients with advanced-stage nonsmall cell lung cancer (NSCLC) and to construct a prediction equation for OS using pretreatment factors.
A pooled data set of 1053 patients from 9 North Central Cancer Treatment Group trials was used. Age, gender, Eastern Cooperative Oncology Group performance status (PS), tumor stage (Stage IIIB vs. Stage IV), body mass index (BMI), creatinine level, hemoglobin (Hgb) level, white blood cell (WBC) count, and platelet count were evaluated for their prognostic significance in both univariate and multivariate analyses by using a Cox proportional-hazards model.
Patients who had high WBC counts, low Hgb levels, PS >0, BMI < 18.5 kg/m2, and TNM Stage IV disease had significantly worse TTP and OS. Patients who had Stage IV disease with a high WBC count had a particularly poor prognosis. An equation to predict the OS of patients with Stage IV NSCLC based on pretreatment PS, BMI, Hgb level, and WBC count was constructed.
In addition to the widely accepted prognostic factors of PS, BMI, and disease stage, both of the readily available laboratory parameters of Hgb level and WBC count were found to be significant prognostic factors for OS and TTP in patients with advanced-stage NSCLC. The authors' prediction equation can be used to evaluate the benefit of a treatment in Phase II trials by comparing the observed survival of a cohort with its expected survival by using the patients' own prognostic factors in place of comparisons with historic data that may have substantially different baseline patient characteristics.
Cancer 08/2006; 107(4):781-92. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: This pooled analysis was performed to examine the impact of pretreatment factors on severe (grade 3 or higher) adverse events (AE) in patients with advanced stage non-small cell lung cancer (NSCLC).
A pooled data set of 1053 participants from nine North Central Cancer Treatment Group clinical trials was used. Age, gender, performance status, tumor stage, body mass index, serum creatinine levels, hemoglobin levels, white blood cell counts, and platelet counts were evaluated univariately and multivariately using logistic regression. The magnitude of the effects of the pretreatment factors after adjusting for type of chemotherapy agent (platinum versus no platinum) was explored in the final multivariate model.
Women and older participants had a significantly greater risk for experiencing severe hematologic and non-hematologic AE. Participants with performance status >0 had an increased risk for severe non-hematologic AE. For every one unit (10/L) increase in pretreatment white blood cell count, there was an 11% reduction in the odds of experiencing a severe hematologic AE. The magnitude of these effects on the end points remained similar after adjusting for type of chemotherapy agent.
Pretreatment factors of gender, age, performance status, and hematologic parameters were significant predictors of severe AE among patients with advanced stage NSCLC. This suggests the need to control or adjust for factors that predispose patients to an increased risk of severe AE. These findings can aid in tailoring therapy to individual patients and in the proper design of future clinical trials.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2006; 1(6):556-63. · 4.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine the efficacy and toxicity of oral topotecan and paclitaxel in untreated patients with extensive stage small cell lung cancer (SCLC).
Thirty-eight patients received 1.75 mg/m2 of oral topotecan days 1 to 5 and 175 mg/m2 paclitaxel IV over 3 hours on day 5 (after topotecan) every 4 weeks for 6 cycles. Subcutaneous G-CSF at a dose of 5 microg/kg was then given 24 to 48 hours after the last dose of chemotherapy and daily for 10 days.
All 38 patients were available for toxicity and response analysis. A median of 5 treatment cycles was given, with a range of 1 to 7 cycles. Seventeen (45%) patients received at least 6 cycles of treatment. The most common severe adverse events were neutropenia (42.1%), leukopenia (34.2%), thrombocytopenia (18.4%), nausea (18.4%), diarrhea (13.2%), and fatigue (13.2%). Two grade 5 treatment-related evens were seen. The median overall survival was 9.1 month (95% CI: 7.5-13.0 months), with a 1-year survival estimate of 44.7% (95% CI: 31.4-63.7%) and a 2-year survival rate of 5.3% (95% CI: 1.4-20.3%). The median time to progression was 5.0 months (95% CI: 3.8-6.6 months), with a 1-year progression-free rate of 5.8% (95% CI: 1.5-22.2%) and a 2-year progression-free rate of 2.9% (95% CI: 0.4-19.9%). The estimated confirmed response rate was 52.9%.
This regimen has shown similar antitumor activity to that achieved with standard therapy. Because of unacceptable toxicity and cost, we do not recommend this regimen in a palliative setting.
American journal of clinical oncology 07/2006; 29(3):246-51. · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Previous studies suggest that the combination of docetaxel and capecitabine are worthy of further testing in patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. We therefore undertook this phase II study to test this combination in a multi-institutional, first-line clinical trial.
Forty-four eligible patients with histologic or cytologic confirmation of the above malignancy were recruited. The cohort had Eastern Cooperative Oncology Group performance scores of 0, 1 and 2 in 59%, 39% and 2% of patients, respectively. Median age was 57 years (range 32-77 years). Adequate organ function was a requirement for study entry. All patients were prescribed docetaxel 75 mg/m2 intravenously on day 1 and capecitabine 825 mg/m2 orally twice a day on days 1-14 of a 21-day cycle.
The tumor response rate was 39% [95% confidence interval (CI) 23% to 55%]. There were two complete responses and the rest were partial. Median survival was 9.4 months (95% CI 6.3-10.7 months) and median time-to-tumor progression was 4.2 months (95% CI 3.6-5.6 months). There was one treatment-related death from a myocardial infarction and dysrhythmia. Commonly occurring grade 3 adverse events included neutropenia (11 patients), infection (five patients), constipation (three patients), thrombosis (three patients), dyspnea (three patients) and hand-foot syndrome (three patients). In addition, 24/45 patients developed grade 4 neutropenia.
The regimen docetaxel and capecitabine shows activity in patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. This regimen merits further study.
Annals of Oncology 05/2006; 17(4):652-6. · 7.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: A one-stage phase II trial was conducted to assess the tumor response rate and toxicity profile of single agent oral vinorelbine as first or second-line chemotherapy for women at least 65 years of age with metastatic breast cancer.
Twenty-five patients with metastatic breast cancer aged > or = 65 years of age were enrolled to receive oral vinorelbine on a weekly basis. The oral vinorelbine was given at 60 mg/m2 weekly for the first four doses and was increased to 70 mg/m2 for the subsequent administrations if there was no grade 4 neutropenia or no more than one episode of grade 3 neutropenia. Therapy was continued until progression or intolerable toxicity.
Twenty-five patients were included and evaluable for analysis. One patient (4%) achieved a partial response (PR) that lasted for more than 13 months. Two additional patients remained stable for at least 6 months for a clinical benefit rate (PR + stable disease) of 12%. The 1-year survival rate was estimated to be 48% (95% CI 30% to 74.5%). Median time to progression was estimated to be 4.7 months (95% CI 2.0-5.5 months) and the 9-month disease progression-free rate was estimated to be 8% (95% CI 30.9% to 74.5%). The treatment was fairly well tolerated with grade 3 neutropenia in 12.5%, fatigue in 12.5% of the patients, and grade 2 neuromotor and neurosensory toxicities in 12.5% and 8.3%, respectively.
Oral vinorelbine as a single agent at these dose and schedule in this population of women > or = 65 years is well tolerated but has a low level of objective efficacy for the treatment of metastatic breast cancer.
Annals of Oncology 04/2006; 17(4):623-9. · 7.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: Vasomotor hot flashes are a common problem in menopausal women. Given concerns regarding estrogen and/or combined hormonal therapy, other treatment options are desired. Prior trials have confirmed that progestational agents and newer antidepressants effectively reduce hot flashes. This current trial compared a single intramuscular dose of medroxyprogesterone acetate (MPA), depot preparation, versus daily oral venlafaxine as treatment for hot flashes.
Women with bothersome hot flashes were entered onto this trial, were randomly assigned to treatment, and then had a baseline week where hot flash scores were recorded without treatment. They were then treated and observed for 6 weeks; daily diaries were used to measure hot flash frequencies and severities. There were 109 patients per each arm randomly assigned to receive MPA 400 mg intramuscularly for a single dose versus venlafaxine 37.5 mg per day for a week, then 75 mg per day.
During the sixth week after random assignment, hot flash scores were reduced by 55% in the venlafaxine arm versus 79% in the MPA arm (P < .0001). In an intention-to-treat analysis, 46% of venlafaxine patients (50 of 109) compared with 74% of the MPA patients (81 of 109) had a decrease in hot flashes by more than 50% from baseline (P < .0001). Less toxicity was reported in the MPA arm.
A single MPA dose seems to be well tolerated and more effectively reduces hot flashes than does venlafaxine.
Journal of Clinical Oncology 04/2006; 24(9):1409-14. · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: The efficacy and tolerability of 2 different schedules of paclitaxel/carboplatin/trastuzumab for HER2-overexpressing metastatic breast cancer (MBC) were evaluated in this parallel multicenter phase II trial.
Patients received every-3-week therapy (n = 43) consisting of a 200 mg/m(2) dose of paclitaxel/carboplatin area under the curve (AUC) of 6 mg/mL per minute and trastuzumab (an initial 8 mg/kg dose and subsequent 6 mg/kg doses) administered every 21 days for 8 cycles or weekly therapy (n = 48) consisting of an 80-mg/m(2) dose of paclitaxel/carboplatin AUC of 2 mg/mL per minute for 3 of 4 weeks, with weekly trastuzumab (an initial 4-mg/kg dose and subsequent 2-mg/kg doses) administered every 4 weeks for 6 cycles. Trastuzumab was continued until disease progression or unacceptable toxicity. HER2 status was confirmed by a central laboratory review.
The overall response rate (ORR) with every-3-week therapy was 65% (90% confidence interval [CI], 51%-77%), with a median time to disease progression of 9.9 months and median overall survival (OS) time of 2.3 years. The ORR with weekly therapy was 81% (90% CI, 70%-90%), with a median time to disease progression of 13.8 months and a median OS time of 3.2 years. Hematologic and nonhematologic toxicities occurred significantly less frequently with weekly therapy versus every-3-week therapy: grade 3/4 neutropenia (52% vs. 88%); grade 3 thrombocytopenia (4% vs. 30%); and grade 3 neurosensory toxicity (2% vs. 19%), respectively.
Every-3-week and weekly regimens of paclitaxel/carboplatin/trastuzumab are highly active in women with HER2-overexpressing MBC. However, fewer patients developed severe neutropenia, leukopenia, or thrombocytopenia with the weekly schedule.
Clinical Breast Cancer 01/2006; 6(5):425-32. · 2.42 Impact Factor
[show abstract][hide abstract] ABSTRACT: A Phase III trial was conducted by the North Central Cancer Treatment Group to determine whether chemotherapy (etoposide and cisplatin) plus either twice-daily radiotherapy (BIDRT) or once-daily radiotherapy (QDRT) resulted in a better outcome for patients with limited-stage small cell lung carcinoma (LD-SCLC). No difference in survival was identified between the two arms. The current analysis examined the relation between age and outcome for patients treated during this trial.
The current study included 263 patients with LD-SCLC and an Eastern Cooperative Oncology Group performance status of < or = 2 who were randomized to receive QDRT or split-course BIDRT. The outcomes of the 209 (79%) younger patients (age < 70 years old) were compared with the 54 (21%) elderly patients (age > or = 70 years old).
Elderly patients presented with significantly greater weight loss and poorer performance status. The 2-year and 5-year survival rates were 48% and 22% for younger patients compared with 33% and 17% for older patients (P = 0.14). One specific toxicity (i.e., Grade > or = 4 pneumonitis [according to National Cancer Institute Common Toxicity Criteria]) occurred in 0% of those patients age < 70 years compared with 6% of older patients (P = 0.008). Grade 5 toxicity occurred in 1 of 209 (0.5%) patients age < 70 years compared with 3 of 54 (5.6%) older patients (P = 0.03).
Despite having more weight loss, poorer performance status, increased pulmonary toxicity, and more deaths due to treatment, survival was not found to be significantly worse in older individuals. Fit elderly patients with LD-SCLC can receive combined-modality therapy with the expectation of relatively favorable long-term survival. Future research should focus on ways to decrease toxicity especially in the elderly.
Cancer 07/2005; 103(11):2349-54. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: This 2-stage, phase II cooperative group trial examined the efficacy and toxicity of 1000 mg/m2 gemcitabine plus 25 mg/m2 cisplatin weekly for 3 weeks and repeated every 28 days for patients with previously treated metastatic breast cancer.
Eligible patients had to have measurable metastatic disease. Progression on prior treatment with at least 1 chemotherapy program for metastatic disease and 1 prior anthracycline and/or taxane-containing regimen in either the metastatic or adjuvant setting was required. Patients who had received more than 2 chemotherapy treatments were not eligible for this study.
Fifty-eight eligible patients were entered on this 2-stage study. A 38% incidence of grade 4 thrombocytopenia observed in the first stage of accrual required lowering the chemotherapy doses to 800 mg/m2 gemcitabine plus 20 mg/m2 cisplatin weekly for the first 3 weeks of a 4-week cycle during the second stage of the study. The overall response rate was 29% (95% confidence interval [CI], 11-52%) among patients receiving the original study dose and 32% (95% CI, 18-50%) for patients receiving the lower dose. In the original- and lower-dose groups, median time to progression was 30.7 weeks (95% CI, 12.7-43.4 weeks) and 26.0 weeks (95% CI, 19.0-32.1 week), respectively. Median survival of the original- and low-dose groups was 67.9 weeks (95% CI, 42.3-90.6 weeks) and 54.1 weeks (95% CI, 41.6-73.6 weeks), respectively. Hematologic toxicities were more manageable in the lower-dose group, whereas the nonhematologic toxicity profile was similar in the 2 dose groups.
The response rate of this combination of gemcitabine and cisplatin is similar to that reported by other investigators but may not differ substantially from reports with single-agent gemcitabine in this patient population. The original dose level we used had unacceptable toxicity, which required lowering the doses of both gemcitabine and cisplatin by 20% to achieve acceptable toxicity and preserve clinical activity.
American journal of clinical oncology 05/2005; 28(2):195-200. · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine whether weekly epoetin alfa could improve hemoglobin (HgB) levels, reduce RBC transfusions, and improve quality of life (QOL) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy.
This double-blind, placebo-controlled study randomly assigned patients to placebo or epoetin alfa (Ortho Biotech, Bridgewater, NJ) 40,000 U subcutaneous weekly for 16 weeks. QOL, HgB, and RBC transfusions were measured pretreatment and monthly.
The study accrued 344 patients; 330 were assessable for efficacy and 305 were assessable for QOL. Placebo-treated patients had a mean increase in HgB of 0.9 g/dL (range, -3.8 to +5.3) compared with 2.8 g/dL (range, -2.2 to +7.5) for epoetin-treated patients (P < .0001). During the study, 31.7% of placebo-treated patients achieved a > or = 2 g/dL HgB increase compared with 72.7% of epoetin-treated patients (P < .0001). The incidence of RBC transfusion for placebo and epoetin treatment arms was 39.6% and 25.3% (P = .005), respectively. The placebo group received 256 units of RBCs compared with 127 units in the epoetin group (P < .0001). The incidence of toxicity in the groups was similar. Changes in the average QOL scores from baseline to the end of the study were similar in the two groups (P = not significant). The HgB responders (irrespective of treatment arm) had a mean change in Functional Assessment of Cancer Therapy (FACT) fatigue score from a baseline of +5.1 compared with -2.1 for the nonresponders (P = .006).
Epoetin alfa significantly improved HgB and reduced transfusions in this patient population. These results support the use of weekly epoetin alfa as an ameliorative agent for cancer-related anemia.
Journal of Clinical Oncology 04/2005; 23(12):2606-17. · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: A phase II multi-institutional clinical trial conducted to evaluate the efficacy and tolerability of docetaxel and carboplatin as first-line therapy for women with metastatic breast cancer.
Patients had histologically confirmed metastatic breast cancer with at least one measurable lesion. Prior adjuvant chemotherapy was permitted, provided that at least 12 months had elapsed between any prior taxane and platinum therapy. Patients received docetaxel 75 mg/m(2) with carboplatin AUC 6 mg/ml.min every 21 days until disease progression or prohibitive toxicity.
All 53 patients enrolled were evaluable for response and toxicity. Median number of cycles delivered was 6. Overall response rate was 60%, with 3 complete responses (6%) and 29 partial responses (54%). Median time to disease progression was 9.6 months. Median survival time was 20.4 months. Myelosuppression was the predominant toxicity, with grade 3 or 4 neutropenia occurring in 94% of patients and 15% of patients experiencing febrile neutropenia. The overall incidence (grades 1-3) of neurosensory toxicity was 57% and neuromotor toxicity was 25%, respectively, with grade 3 toxicity occurring in 4% of patients each.
The combination of docetaxel and carboplatin is highly active in metastatic breast cancer. Prophylactic growth factor support is recommended in any further evaluation of this combination in the treatment of patients with breast cancer.
[show abstract][hide abstract] ABSTRACT: Intergroup Trial N9741 evaluated 5-fluorouracil (5-FU)/leucovorin (LV) administered in conjunction with either irinotecan or oxaliplatin in the first-line treatment of advanced colorectal carcinoma (CRC). The current report describes two treatment arms that were withdrawn from the protocol due to unexpected treatment-related toxicities and a high mortality rate. The complications observed in these arms highlight the importance of aggressive and immediate supportive care in the management of digestive toxicity.
In Trial N9741, patients were randomly assigned to receive one of the following six regimens: 1) irinotecan plus bolus 5-FU/LV (Arm A); 2) sequential irinotecan plus bolus 5-FU/LV (Arm B); 3) bolus 5-FU/LV only (Mayo Clinic regimen; Arm D); 4) oxaliplatin plus bolus 5-FU/LV (Arm E); 5) oxaliplatin plus infusional 5-FU/LV (Arm F); or 6) oxaliplatin plus irinotecan (Arm G). In the current study, the authors investigated treatment-related toxicity in patients who received either of the two combination regimens containing daily bolus 5-FU (i.e., patients in Arm B or Arm E).
Sixty-one and 47 patients were enrolled in Arm B and Arm E, respectively. Diarrhea and neutropenia were the most common toxicities in both groups. Five patients in Arm B (8.2%) and 4 patients in Arm E (8.5%) died within 60 days of study entry. All fatal toxicities occurred within 15 days of treatment administration, and all deaths were associated with the simultaneous occurrence of multiple symptoms, which were dominated by Grade > or = 3 diarrhea.
Combination regimens containing daily bolus 5-FU/LV and oxaliplatin or irinotecan can be associated with severe gastrointestinal toxicity and high mortality rates. Therefore, the authors recommend the use of more tolerable infusional 5-FU-based regimens in the treatment of metastatic CRC.
Cancer 11/2004; 101(10):2170-6. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNFalpha), and interleukin-6 (IL-6) have been implicated in the cancer anorexia/weight loss syndrome. However, previous smaller studies have yielded conflicting results as to whether circulating, serum concentrations of these cytokines are in fact elevated. As the translational component of a large multi-institutional trial, this study assessed the clinical value of serum concentrations of these cytokines in patients with this syndrome.
Patients with incurable cancer with anorexia and/or weight loss were eligible. All underwent weekly weight measurements and appetite assessment for the first month and then monthly assessments thereafter. Serum was obtained at baseline and at 1 month, and all three cytokines were measured with the Immunolite assay.
A total of 118 patients participated. At baseline, 99%, 54%, and 47% of patients' samples had undetectable IL-1beta, TNFalpha, and IL-6, respectively. Similar results were obtained at 1 month. No correlations were observed between serum cytokine concentrations and changes in weight or appetite. Baseline serum IL-6 predicted a diminished survival but only after adjustment for age and cancer site.
Serum concentrations of IL-1beta, TNFalpha, and IL-6, as measured in this study, provide data of limited clinical value for patients with the cancer anorexia/weight loss syndrome.
Supportive Care Cancer 10/2004; 12(9):640-4. · 2.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: This Phase III study was performed to determine whether twice-daily (b.i.d.) radiotherapy (RT) resulted in better survival than once-daily (q.d.) RT for patients with limited-stage small-cell lung cancer (LD-SCLC).
A total of 310 patients with LD-SCLC initially received three cycles of etoposide and cisplatin. Subsequently, the 261 patients without significant progression were randomized to two cycles of etoposide and cisplatin plus either q.d. RT (50.4 Gy in 28 fractions) or split-course b.i.d. RT (24 Gy in 16 fractions, a 2.5-week break, and 24 Gy in 16 fractions) to the chest. Patients then received a sixth cycle of etoposide and cisplatin followed by prophylactic cranial RT.
Follow-up ranged from 4.6 to 11.9 years (median, 7.4 years). The median survival and 5-year survival rate from randomization was 20.6 months and 21% for patients who received q.d. RT compared with 20.6 months and 22% for those who received b.i.d. RT (p = 0.68), respectively. No statistically significant differences were found in the rates of progression (p = 0.68), intrathoracic failure (p = 0.45), in-field failure (p = 0.62), or distant failure (p = 0.82) between the two treatment arms. No statistically significant difference was found in the overall rate of Grade 3 or worse (p = 0.83) or Grade 4 or worse toxicity (p = 0.95). Grade 3 or worse esophagitis (p = 0.05) was more common in the b.i.d. arm. Grade 5 toxicity occurred in 4 (3%) of 130 patients who received b.i.d. RT compared with 0 (0%) of 131 who received q.d. RT (p = 0.04).
Although this study did not demonstrate an advantage to split-course b.i.d. RT, the long-term survival was favorable, likely reflecting the positive influences of concurrent combined modality therapy and prophylactic cranial RT.
International Journal of Radiation OncologyBiologyPhysics 08/2004; 59(4):943-51. · 4.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: Some patients with colon cancer have a high risk of local recurrence postoperatively. This trial was undertaken to determine whether radiation therapy added to an adjuvant chemotherapy regimen improves outcome in high-risk patients.
Patients with resected colon cancer with tumor adherence or invasion of surrounding structures, or with T3N1 or T3N2 tumors of the ascending or descending colon were randomly assigned to receive fluorouracil and levamisole therapy with or without radiation therapy. Patients who received chemotherapy and radiation therapy (chemoRT) received 45 to 50.4 Gy in 25 to 28 fractions beginning 28 days after starting chemotherapy. Patient enrollment was terminated because of slow accrual after 222 patients enrolled (original goal was 700 patients); 187 patients were assessable.
Overall 5-year survival was 62% for chemotherapy patients and 58% for chemoRT patients (P >.50); 5-year disease-free survival was 51% for both groups (P >.50). Toxicity (>/= grade 3) occurred in 42% of chemotherapy patients and 54% of chemoRT patients (P =.04). Leukopenia (>/= grade 3) occurred in 10% of chemotherapy patients and 22% of chemoRT patients (P =.02). No significant difference in nonhematologic toxicity (>/= grade 3) was observed between chemoRT and chemotherapy patients (35% v 44%; P =.26).
Patients who received chemotherapy or chemoRT had similar overall survival and disease-free survival. Toxicity was higher among chemoRT patients. These results must be interpreted with caution because of the high number of ineligible patients and the limited power of the study to detect potentially meaningful differences.
Journal of Clinical Oncology 08/2004; 22(16):3277-83. · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: A pressing need exists for agents active against anthracycline- or taxane-refractory metastatic breast cancer (MBC), or both. Previous clinical trials suggested that irinotecan might have such activity. We conducted this multicenter phase II study to assess efficacy and tolerability of two irinotecan schedules.
MBC patients who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline- or taxane-based regimen, were randomly assigned to irinotecan in 6-week cycles comprising 100 mg/m(2) weekly for 4 weeks, then a 2-week rest (weekly) or 240 mg/m(2) every 3 weeks.
The weekly arm had 52 assessable patients; the every-3-weeks arm had 51 assessable patients. In the weekly arm, the objective response (complete regression [CR] + partial regression [PR]) rate was 23% (one CR, 11 PR; 95% CI, 13% to 37%). Median response duration was 4.9 months (range, 1.9 to 15.9 months), and median overall survival was 9.7 months (95% CI, 8.0 to 14.2 months). In the every-3-weeks arm, the objective response rate was 14% (nine PR; 95% CI, 6% to 26%), median response duration was 4.2 months (range, 3.1 to 13.9 months), and median overall survival was 8.6 months (95% CI, 7.0 to 12.3 months). Treatment generally was well tolerated, especially in the weekly arm. Grade 3 to 4 adverse events with > or = 10% incidence included neutropenia (29%) and diarrhea (17%) in the weekly arm and neutropenia (36%), vomiting (20%), dyspnea (18%), nausea (16%), and diarrhea (12%) in the every-3-weeks arm.
Irinotecan is active with good tolerability in refractory MBC. Irinotecan (especially weekly) warrants additional study as monotherapy and in combination regimens in this setting.
Journal of Clinical Oncology 07/2004; 22(14):2849-55. · 18.04 Impact Factor