Outcomes and toxicity in african-american and caucasian patients in a randomized adjuvant chemotherapy trial for colon cancer.

BACKGROUND: Previous studies have demonstrated that African-Americans with colon cancer have worse overall and stage-specific survival rates than Caucasians. Such differences could reflect variation in access to health care, in tumor biology, or in treatment efficacy. Little is known about potential differences in chemotherapy-related toxicities between African-Americans and Caucasians. In this study, we examined survival and toxic effects among African-American and Caucasian patients enrolled in a large, randomized phase III trial of adjuvant chemotherapy for resected colon cancer. METHODS: We analyzed data on 3380 patients (344 African-Americans and 3036 Caucasians) enrolled in a randomized trial of adjuvant 5-fluorouracil-based chemotherapy in patients with stage II (high risk) and stage III colon cancer to evaluate differences in outcomes and toxicity. We compared disease-free survival (DFS) and overall survival (OS) between African-Americans and Caucasians by the Kaplan-Meier method, computed Cox proportional hazards by multivariable analysis, and compared treatment-related toxicity rates by Fisher's exact test. All statistical tests were two-sided. RESULTS: We found no differences in DFS or OS between African-American and Caucasian patients. Five-year DFS was 57% (95% confidence interval [CI] = 52% to 62%) for African-Americans and 58% (95% CI = 56% to 60%) for Caucasians (P =.15), and 5-year OS was 65% (95% CI = 60% to 70%) for African-Americans and 66% (95% CI = 64% to 68%) for Caucasians (P =.38). On multivariable analysis, no statistically significant difference in disease recurrence or death was detected between the racial/ethnic groups (hazard ratios for African-Americans versus Caucasians: disease recurrence = 1.1, 95% CI = 0.9 to 1.3; death = 1.1, 95% CI = 0.9 to 1.3). Treatment-related toxicity differed between the African-American and Caucasian patients, with African-Americans experiencing statistically significantly lower rates of diarrhea (P<.001), nausea (P<.001), vomiting (P =.01), stomatitis (P<.001), and overall toxicity (P =.005). CONCLUSIONS: In this study of patients with similar access to health care resources and treatment with adjuvant chemotherapy, we found similar 5-year DFS and OS in African-Americans and Caucasians with stage II and III colon cancer. The two groups derived similar benefits from adjuvant chemotherapy. Moreover, African-Americans appeared to experience less treatment-related toxicity.

Impact of body mass index on outcomes and treatment-related toxicity in patients with stage II and III rectal cancer: findings from Intergroup Trial 0114.

PURPOSE: To study the relationship between body mass index (BMI) and rates of sphincter-preserving operations, overall survival, cancer recurrence, and treatment-related toxicities in patients with rectal cancer. PATIENTS AND METHODS: We evaluated a nested cohort of 1,688 patients with stage II and III rectal cancer participating in a randomized trial of postoperative fluorouracil-based chemotherapy and radiation therapy. RESULTS: Obese patients were more likely to undergo an abdominoperineal resection (APR) than normal-weight patients (odds ratio, 1.77; 95% CI, 1.27 to 2.46). When analyzed by sex, increasing adiposity in men was a strong predictor of having an APR (P <.0001). Obese men with rectal cancer were also more likely than normal-weight men to have a local recurrence (hazard ratio [HR], 1.61; 95% CI, 1.00 to 2.59). In contrast, obesity was not predictive of cancer recurrence in women, nor was BMI predictive of overall mortality in either men or women. Underweight patients had an increased risk of death (HR, 1.43; 95% CI, 1.08 to 1.89) compared with normal-weight patients but no increase in cancer recurrences. Among all study participants, obese patients had a significantly lower rate of grade 3 to 4 leukopenia, neutropenia, and stomatitis and a lower rate of any grade 3 or worse toxicity when compared with normal-weight individuals. CONCLUSION: Increasing BMI in male patients with rectal cancer is associated with a decreased likelihood of sphincter preservation and a higher chance of local recurrence. For both men and women, overweight and obese patients experience less toxicity associated with adjuvant chemoradiotherapy, suggesting that actual body weight dosing of fluorouracil for obese patients is justified.

Referral patterns and adjuvant chemotherapy use in patients with stage II colon cancer.

BACKGROUND: Little is known about the actual rate of use of adjuvant chemotherapy in stage II colon cancer and about referral patterns that give patients access to this treatment. PATIENTS AND METHODS: We searched the tumor registry at Baylor University Medical Center at Dallas to identify patients with stage II colon cancer who underwent resection between 1995 and 2003. The rates of referral to medical oncology and adjuvant chemotherapy use were calculated and potential predictive variables were analyzed using univariate and multivariate techniques. RESULTS: We identified 287 patients with stage II colon cancer. A total of 160 patients (56%) were referred to a medical oncologist. Eighty patients (28%) received adjuvant chemotherapy. Age < 50 years, private insurance status, lower comorbidity score, higher T stage, and poor tumor differentiation were significant predictors of adjuvant chemotherapy use (P

Novel agents for the treatment of adenocarcinoma of the pancreas.

Pancreatic cancer is a particularly challenging malignancy, given its usually advanced stage at diagnosis and its rather limited treatment options. Gemcitabine has been standard therapy for advanced pancreatic cancer for well over a decade. The addition of capecitabine or erlotinib to gemcitabine has resulted in modestly improved, although still poor, overall survival. The majority of the recently completed randomized trials, however, have failed to demonstate an improvement of newer treatments over single-agent gemcitabine. Efforts currently underway center on new cytotoxic chemotherapy drugs, as well as novel targeted agents inhibiting various molecular pathways. Newly discovered proteins and cellular elements involved in tumor growth and invasion are potential therapeutic targets, and have become the focus of current trials, as well as future clinical trials. A better understanding of the biology of the disease at the basic science level, and epidemiology and risk factors from a public-health perspective, are needed. Continued research is clearly warranted with the goal of improving survival and optimizing treatment outcomes in locally advanced and metastatic pancreatic cancer.

The combination of capecitabine and thalidomide in previously treated, refractory metastatic colorectal cancer.

BACKGROUND: With the increasing survival of patients with metastatic colorectal cancer (CRC) there is a growing need for effective second- and third-line agents. We conducted a multicenter, phase II study to examine the combination of capecitabine and thalidomide (Cape/Thal) in patients with refractory metastatic CRC. METHODS: Patients with previously treated stage IV CRC were eligible. Treatment consisted of capecitabine at 1,000 mg/m2 po BID for 14 days every 3 weeks and thalidomide, starting at 200 mg po QD continuously. Thalidomide was escalated individually to 600 mg po QD as tolerated. We analyzed overall survival (OS), progression-free survival, response, and toxicity rates. RESULTS: Thirty-four eligible patients were enrolled. The median age was 57 years, and most patients had a normal performance status (65%). All patients had received prior chemotherapy and 19 (56%) had received 2 or 3 prior regimens. The median number of Cape/Thal cycles administered was 3 (range, 1-15). Grade 3/4 toxicities included fatigue (15%), venous thromboembolic events (12%), somnolence (12%), and constipation (9%). Grade 2 hand-foot syndrome occurred in 5 (15%) patients. There were no radiographic responses; 13 patients (38%) achieved stable disease. The median PFS was 2.6 months (95% confidence interval [CI] = 2.2-3.9) and the median OS was 7.1 month (95% CI = 5.2-12.0). CONCLUSIONS: Though well-tolerated, the combination of capecitabine and thalidomide was not associated with objective tumor responses in a population of patients with previously treated metastatic CRC.

Lack of efficacy of streptozocin and doxorubicin in patients with advanced pancreatic endocrine tumors.

BACKGROUND: The combination of streptozocin and doxorubicin has been considered the standard palliative chemotherapy regimen in patients with advanced pancreatic endocrine tumors (PETs). However, a recent review failed to confirm high antitumor activity in patients with advanced PETs. METHODS: We retrospectively reviewed the records of 16 consecutive patients who received streptozocin and doxorubicin for advanced PETs at Dana Farber/Partners Cancer Care institutions. Baseline patient characteristics, radiographic response to therapy, treatment-related toxicity, progression-free and overall survival were analyzed. RESULTS: One patient demonstrated an objective partial response to therapy (objective response rate [ORR], 6%; 95% confidence interval [CI], 0-18%). Six patients achieved stable disease (38%; 95% CI, 14-62%) and 9 patients demonstrated disease progression on initial restaging (56%; 95% CI, 33-77%). The median progression-free survival and overall survival were 3.9 months (95% CI, 2.8-8.8) and 20.2 months (95% CI, 9.7-37.4), respectively. CONCLUSIONS: In this retrospective cohort, the combination of streptozocin and doxorubicin failed to demonstrate substantial antitumor activity in patients with advanced PET. Our findings underscore the need for new therapeutic options in this patient population.

Positron emission tomography with 18F-fluorodeoxyglucose to predict pathologic response after induction chemotherapy and definitive chemoradiotherapy in head and neck cancer.

BACKGROUND: Conventional imaging is limited in identifying persistent disease after organ-preserving therapy for patients with advanced squamous cell carcinoma of the head and neck (SCCHN). We studied the accuracy of positron emission tomography (PET) with (18)F-fluoro-2-deoxy-D-glucose (FDG-PET) in restaging disease in patients with SCCHN after they had undergone induction chemotherapy (ICT) followed by chemoradiotherapy (CRT). METHODS: Forty patients with advanced SCCHN were treated with ICT followed by CRT. FDG-PET imaging was performed to assess for residual cancer at the primary site and in nodal metastases. Two nuclear medicine physicians interpreted PET scans in random sequence. Test characteristics were calculated with pathologic analysis or clinical recurrence as the standard. RESULTS: After induction chemotherapy, PET imaging had a sensitivity of 100% and specificity of 65% for detecting persistent disease at the primary tumor site. After ICT and CRT were completed, the sensitivity and specificity of PET imaging were 67% and 53%, respectively, for detecting occult disease in cervical lymph nodes. CONCLUSIONS: FDG-PET imaging showed some correlation with pathologic response after ICT and CRT in patients with advanced SCCHN. The use of FDG-PET warrants further investigation in this setting.