Phase I study of combined radiation, hyperthermia and intra-arterial carboplatin for local recurrence of cervical cancer.

BACKGROUND: Patients with cervical cancer who develop pelvic recurrence after primary surgery are usually treated with radiation-based therapy. However, their prognoses are dismal. We conducted a phase I study of combined radiation, hyperthermia and intra-arterial (IA) carboplatin for local recurrence of cervical cancer. PATIENTS AND METHODS: Patients with local recurrence of cervical cancer without extrapelvic recurrence were included in this study. Carboplatin was given as a 5-min IA infusion without hydration just before pelvic radiation every day. External pelvic irradiation (1.8 Gy/day for 28 days) was performed according to local standard schedules. After 20 Gy had been administered, hyperthermia was performed once a week with a radio frequency heating system for four cycles. RESULTS: Fifteen patients were entered through the four dose levels of carboplatin. The maximum tolerated dose was determined to be 25 mg/m(2 )and the dose-limiting toxicities were leukocytopenia, neutrocytopenia and diarrhea. Grade 3/4 leukocytopenia and diarrhea were observed in nine (60%) and three (20%) of 15 patients. Tumor responses included five complete responses and nine partial responses, and the overall response rate was 93.3% (14 of 15) (95% confidence interval 59.4% to 100%). Tumor reductions were observed only at 20 Gy in 10 cases of 14 responders (71.4%). CONCLUSION: The combination therapy of radiation, hyperthermia and IA carboplatin is safe and well-tolerated for locally recurrent cervical cancer.     

Simultaneous radio‐ and chemotherapy for squamous cell carcinoma of the head and neck in daily clinical practice: 5 years experience in a University Hospital

Several randomized studies and meta‐analyses have shown that simultaneous radio‐ and chemotherapy prolongs survival in patients with unresectable squamous cell carcinoma of the head and neck as compared with conventional radiotherapy. We assessed the feasibility and effectiveness of simultaneous radiotherapy (35 × 2 Gy) and chemotherapy [cisplatinum 100 mg/m² or carboplatin (AUC 6) on days 1, 22 and 43] in daily clinical practice in a cohort of 87 patients treated at our institute between 1998 and 2002. Eighty patients completed radiotherapy according to schedule. Eighty patients received two courses of chemotherapy and 50 patients three courses. Nephrotoxity, bone marrow suppression and ototoxicity were the most frequent side‐effects. Median weight loss was 8.5%. Median survival was 15 months and 44% of the patients were alive at 2 years. Patients receiving three courses of chemotherapy had a better survival than patients receiving two or less courses. Treatment with simultaneous radio‐ and chemotherapy for advanced head and neck cancer is a demanding, but feasible treatment in daily clinical practice. Survival seems to be comparable with the results achieved in patients selected for clinical trials.     

同步放化疗与新辅助化疗术前用药在局部中晚期宫颈癌治疗中的临床疗效评价

目的:比较同步放化疗与新辅助化疗术前用药在治疗局部中晚期宫颈癌的临床疗效。方法:选择2002年3月至2005年3月我院收治的42例ⅠB2～ⅡB期宫颈癌患者,其中21例同步放化疗,21例新辅助化疗。两组化疗方案相同,鳞癌:顺铂(DDP)+博来霉素;腺癌:DDP+5-氟尿嘧啶(5-Fu)+丝裂霉素(MMC)。同步放化疗组化疗期间配合放疗,采用腔内近距离放疗。同步放化疗、新辅助化疗结束后选择合适时间手术。观察两组间的近期疗效、手术率及手术切缘阴性情况、毒副反应、远期疗效(1、3、5年生存率)。结果:两组间近期疗效差异无统计学意义(P>0.05)、手术率及手术切缘阴性率差异有高度统计学意义(P<0.01)。血液和胃肠道毒副反应差异无统计学意义(P>0.05),晚期并发症放射性直肠炎和膀胱炎差异有高度统计学意义(P<0.01)。1年、3年生存率差异无统计学意义(P>0.05),而5年生存率同步放化疗组高于新辅助化疗组(P<0.05)。结论:同步放化疗术前用药治疗局部中晚期宫颈癌优于新辅助化疗。     

A phase II randomized double blinded trial evaluating the efficacy of curcumin with pre-operative chemoradiation for rectal cancer

BackgroundIn vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome.MethodsFrom 2008–2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m² twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. Blood samples taken pre- and 1-hour post-ingestion and tissue biopsies (both collected at CRT week 2) were analyzed for pharmacokinetics. The primary outcome was surgical pCR rate.ResultsOf 22 enrolled patients, 15 received curcumin. Median age was 61 years and the majority were male (n=13; 59%). The median serum curcumin concentrations before (3.04 ng/mL; range, 1.24–18.88 ng/mL) and 1 hour after (3.32 ng/mL; range, 0.84–5.36 ng/mL) curcumin intake did not differ significantly (P=0.33). Serum curcumin concentrations both increased and decreased 1-hour post-administration (range as percentage of baseline: 8.8–258.1%). Twelve curcumin patient tissue biopsies had median curcumin concentration of 33.7 ng/mg tissue (range, 0.1–4,765.7 ng/mg). Two placebo and 1 curcumin patient achieved pCRs (P=0.18). One grade 3 toxicity (infection) was experienced.ConclusionsThe addition of curcumin to CRT did not increase pCR rates for LARC patients. The unpredictable bioavailability of curcumin contributes to continued uncertainties regarding curcumin efficacy.Trial RegistrationClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT00745134","term_id":"NCT00745134"}}NCT00745134.     

Pharmacoeconomics of cisplatin-based chemoradiation in cervical cancer: a review

Staphylococcus aureus is a bacterial pathogen responsible for a variety of serious infections and is a frequent cause of nosocomial disease. During the last 60 years, S. aureus has developed increasing in vitro resistance to virtually all antimicrobials. In contrast, vancomycin has maintained a high degree of activity in vitro against this pathogen, although slight changes with in vitro activity could vastly change clinical activity. As a result, vancomycin has become the mainstay of therapy for invasive infections due to methicillin-resistant strains. However, clinical strains of S. aureus with intermediate resistance to vancomycin were reported in 1996, followed in 2002 with reports of isolates that were fully resistant. Although many authorities believe vancomycin remains the drug of choice for most staphylococcal-resistant infections, important issues surrounding its clinical application remain. These include the need for multiple daily dosing, intravenous administration, requirements for serum concentration monitoring, increasing resistance in vitro, modest efficacy rates and (less frequently) treatment-limiting adverse effects. This review addresses these important topics.     

T-level downstaging and complete pathologic response after preoperative chemoradiation for advanced rectal cancer result in decreased recurrence and improved disease-free survival

PURPOSE: Preoperative chemoradiation therapy is used widely in the treatment of rectal cancer. The predictive value of response to neoadjuvant remains uncertain. We retrospectively evaluated the impact of response to preoperative and, specifically, of T-level downstaging, nodal downstaging, and complete pathologic response after chemoradiation therapy on oncologic outcome of patients with locally advanced rectal cancer. METHODS: There were 88 patients with ultrasound Stage T3/T4 midrectal (n = 37) and low rectal (n = 51) cancers (63 males; mean age 62.6 years). All patients were treated by preoperative 5-fluorouracil-based chemotherapy and pelvic radiation followed by surgical resection in six weeks or longer (56 sphincter-preserving resections). RESULTS: T-level downstaging after neoadjuvant treatment was demonstrated in 36 (41 percent) of 88 patients, and complete pathologic response was observed in 16 (18 percent) of the 88. Of the 42 patients with ultrasound-positive nodes, 27 had no evidence of nodal involvement on pathologic evaluation (64 percent). The overall response rate (T-level downstaging or nodal downstaging) was 51 percent. At a median follow-up of 33 months, 86.4 percent of patients were alive. The overall recurrence rate was 10.2 percent (three patients had local and six had metastatic recurrences). Patients with T-level downstaging and complete pathologic response were characterized by significantly better disease-free survival (P = 0.03, P = 0.04) and better overall survival (P = 0.07, P = 0.08), according to Wilcoxons test comparing Kaplan-Meier survival curves. None of the patients with complete pathologic response developed recurrence or died during the follow-up period. CONCLUSION: T-level downstaging and complete pathologic response after preoperative chemoradiation therapy followed by definitive surgical resection for advanced rectal cancer resulted in decreased recurrence and improved disease-free survival. Advanced rectal cancers that undergo T-level downstaging and complete pathologic response after chemoradiation therapy may represent subgroups that are characterized by better biologic behavior.     

What's new in pancreatic cancer treatment?

Pancreatic cancer represents a major challenge to oncologists because of its high chemoresistant nature and dismal outcomes. Conventional therapy for advanced disease relied for a long time on palliative 5‐fluorouracil (5‐FU)‐based chemotherapy, but with unsatisfactory results. The introduction of the novel antimetabolite gemcitabine provides new optimism for patients with advanced pancreatic cancer, as multiple clinical trials have demonstrated the superiority of gemcitabine over 5‐FU and other agents for these patients. The benefits of gemcitabine over conventional therapies include improved response rate and enhanced survival, as well as improvement in disease‐related symptoms and quality of life in these patients. With these data, gemcitabine is widely accepted worldwide as the therapy of choice by many oncologists for advanced pancreatic cancer. The current review presents an overview of the clinical studies of gemcitabine over the past decade for the treatment of patients with advanced pancreatic cancer. Other investigational regimens or uses (e.g., fixed dose‐rate infusion, intraarterial infusion, adjuvant use, chemo‐radiation, etc) are also reviewed.