This study sought to determine whether third line therapy with capecitabine (cap.) could provide any clinical benefit in patients with advanced colorectal cancer who have progressed on 5-Fu combination therapy with both irinotecan and oxaliplatin. Twenty patients who were pretreated with and had progressed on irinotecan+Nordic FLv (5-Fu/leukovorin) and oxaliplatin+c.i. 5-Fu/leukovorin were studied. Cap. was administered at 1000-1250 mg/m2 bid d1-14 q 3 w. Time to progression (TTP) (either radiological or clinical) and overall survival (OS) were estimated with the Kaplan-Meier actuarial method. The median number of administered cap. courses was four. No radiological or biochemical responses were observed. Three patients were classified as having stable disease at three months. Two of these patients had, however, minor radiological progression and a =100% increase in CEA compared to base line. Seventeen patients were classified as having progressive disease during the first three months period. Median TTP and OS were 2.8 months and 6.1 months, respectively. A response rate of =15% for third line cap. in metastatic CRC can be ruled out. Median PFS was limited in the study population. This observation and the few cases with SD at three months, lead us to believe that little or no clinical benefit can be expected from single drug cap. in patients with irinotecan- and oxaliplatin-combination resistant advanced colorectal cancer.
PURPOSE: To evaluate the influence of a H2 receptor antagonist (cimetidine) on survival in patients with colorectal carcinoma, a randomized, controlled pilot study was performed in three university hospitals in Copenhagen, Denmark. METHODS: A total of 192 patients, who had undergone a resection or an exploratory operation for adenocarcinoma of the colon or rectum between May 1988 and May 1991, were enrolled in the study. After a median observation time of 40 months, outcome was noted for each patient concerning cancer-specific mortality rate. RESULTS: In patients operated with curative intent (n = 148), no difference was found in cancer-specific mortality between the two treatments. However, a tendency toward reduction in mortality rate was found in patients with curatively operated Dukes Stage C carcinoma (P = 0.11, log-rank test; difference, 29 percent; 90 percent confidence interval, 2 to 57 percent) in the cimetidine-treated group. In patients with disseminated disease no total difference was found between the two treatment groups. CONCLUSIONS: Cimetidine does not seem to reduce mortality in patients with colorectal cancer, but there seems to be a tendency toward a survival benefit in patients undergoing surgery for Dukes Stage C carcinoma. Results seem to justify trials in this patient category to reveal a benefit of H2 receptor antagonists in adjuvant therapy of colorectal carcinoma.
PURPOSE: At the time of diagnosis, approximately one third of patients with rectal cancer present with advanced disease. In this study we focus on a group of patients with primary advanced rectal cancer considered as not operable. We address various clinical aspects relevant for decision-making in a group of patients in need of palliative care. METHODS: Between January 1997 and December 2001, 4831 consecutive patients with rectal cancer were prospectively registered in the Norwegian Rectal Cancer Registry. In this national population-based cohort, 386 patients (8 percent) without surgical interventions were identified. These patients comprise the study population. Clinical characteristics and survivals were addressed. RESULTS: Patients not surgically treated were significantly older compared with other treatment groups (median age, 80 years; interquartile range, 72-86 vs. median age, 71 years; interquartile range, 62-79 years) (P
The prognosis following radical operation for rectal cancer is still dubious. There is urgent need for effective adjuvant treatment in order to control both local and distant recurrences. During the last years the use of combined adjuvant treatment (radiochemotherapy ) has increased both recurrence-free survival in several randomised trials. The trials are reviewed in this article. Adjuvant treatment has been recommended as standard therapy in the USA since 1990. Following the German national consensus conference in March 1994, adjuvant treatment is now being recommended in Germany as well. In several other countries in Europe adjuvant therapy is routinely being offered to high-risk colorectal cancer patients following the surgical procedure. The experiences and results that now are available ought to be discussed in the near future in order to establish a national consensus in Denmark.
To quantify the clinical consistency of expert panelists' ratings of appropriateness of pre-operative and post-operative chemotherapy plus radiation for rectal cancer.
A panel of nine physicians (two surgeons, four medical oncologists, three radiation oncologists) rated the appropriateness of providing pre-operative and post-operative treatments for rectal cancer, utilizing a modified-Delphi (RAND/UCLA) approach. Clinical scenarios were paired so that each component of a pair differed by only one clinical feature (e.g. tumor stage). A pair of appropriateness ratings was defined as inconsistent when the clinical scenario that should have had the higher (or at least equal) appropriateness rating was given a lower rating. The rate of inconsistency was analyzed for panelists' ratings of pre- and post-operative chemotherapy plus radiation.
The final panel rating was inconsistent for 1.19% of pre-operative scenario pairs, and 0.77% of post-operative scenario pairs. Using the conventional RAND/UCLA definition of appropriateness, the magnitude of the inconsistency would produce inconsistent appropriateness ratings in 0.43% of pre-operative and 0.11% of post-operative scenario pairs. There was significant variation in the rate of inconsistency among individual panelists' final ratings of both pre-operative (range: 0.43-5.17%, P
In Canada, provincial cancer registries have been established to provide rigorous population-based data for patients with colorectal cancer. Databases maintained by regional cancer agencies contain a broader scope of information and have been used as a surrogate source of information for colorectal cancer research. It is unclear whether these data can be reliably extrapolated to all patients affected by colorectal cancer. We sought to determine whether patients included in a referral-based database are systematically different from patients who are not included.
We conducted a retrospective cohort study to compare patients referred to the British Columbia Cancer Agency with those who were not referred. Comparison was based on age, sex and geographic location. We used univariate and logistic regression analysis to identify significant differences between the cohorts.
Univariate analysis demonstrated that the referral and nonreferral cohorts differed in sex, age and geographic location. For patients with rectal cancer, the referral and nonreferral cohorts varied in age and geographic location. Multivariate analysis demonstrated significant differences in age and geographic location but not sex for patients with colon and rectal cancer.
Patients included in the referral database differed in age and geographic location from those included only in the provincial database. Studies using large data sets from referral centres must be interpreted with caution and may not be representative of the entire patient population.
To our knowledge, the genotoxic effects of neoadjuvant chemoradiation therapy on molecular diagnostic testing results are unknown. However, if neoadjuvant treatments were to alter molecular test results, clinical decision-making could be misled. This raises questions about the appropriateness of using posttreatment tumor for testing. To address this, rectal adenocarcinomas both before and after neoadjuvant treatment were evaluated for alterations in KRAS and microsatellite instability (MSI) testing. Neoadjuvant chemoradiation therapy is common in this tumor type, and alterations in these 2 tests would significantly impact management. A total of 17 rectal adenocarcinoma patients with available pretreatment and posttreatment tumor were studied. MSI testing used the revised National Cancer Institute panel of 5 mononucleotide microsatellite repeats, comparing cancers with matched normal control tissues. KRAS codon 12-point and 13-point mutations were examined by polymerase chain reaction amplification and bidirectional sequencing. MSI and KRAS results were unchanged comparing rectal cancer tissue before and after chemoradiotherapy in all 17 patients (P=1.000; 95% CI: 0.3969-2.520). All 17 tumors (100%) were microsatellite stable. KRAS testing identified 12 (72%) wild-type tumors and 5 (28%) codon 12 or 13 mutant tumors with identical KRAS point mutations before and after treatment. The identified MSI and KRAS mutational prevalences parallel those reported in the rectal cancer literature. Neoadjuvant therapy did not alter KRAS codon 12 or 13 or MSI results in rectal adenocarcinoma, providing evidence that either pretreatment biopsy or posttreatment resection tissues are appropriate for testing.
Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation.
The inclusion criteria were resectable T3 and T4 tumors with a circumferential margin of =5 mm on magnetic resonance imaging. The patients were randomized to receive 50.4 Gy in 28 fractions to the tumor and pelvic lymph nodes (arm A) or the same treatment supplemented with an endorectal boost given as high-dose-rate brachytherapy (10 Gy in 2 fractions; arm B). Concomitant chemotherapy, uftoral 300 mg/m2 and L-leucovorin 22.5 mg/d, was added to both arms on treatment days. The primary endpoint was complete pathologic remission. The secondary endpoints included tumor response and rate of complete resection (R0).
The study included 248 patients. No significant difference was found in toxicity or surgical complications between the 2 groups. Based on intention to treat, no significant difference was found in the complete pathologic remission rate between the 2 arms (18% and 18%). The rate of R0 resection was different in T3 tumors (90% and 99%; P=.03). The same applied to the rate of major response (tumor regression grade, 1+2), 29% and 44%, respectively (P=.04).
This first randomized trial comparing 2 radiation doses indicated that the higher dose increased the rate of major response by 50% in T3 tumors. The endorectal boost is feasible, with no significant increase in toxicity or surgical complications.
Comment In: Int J Radiat Oncol Biol Phys. 2013 Jun 1;86(2):212-323642620
Comment In: Int J Radiat Oncol Biol Phys. 2013 Jun 1;86(2):21323642621
Often due to a severe somatic condition of the patient, the presence of perifocal inflammation, anemia, age, it is not possible to perform neoadjuvant chemoradiotherapy for rectal cancer. To improve cancer treatment outcomes in these patients intraoperative intrapelvic chemotherapy with hyperthermia is used at the Centre. In the present study there included 120 patients with rectal cancer at stage T3-4N0-2M0, while 60 patients underwent intraoperative intrapelvic chemotherapy with hyperthermia (cisplatin at a dose of 150 mg, the time of the procedure--60 minutes, the temperature of the perfusate--44-45 degrees C). Conducting of intraoperative intrapelvic chemotherapy with hyperthermia allowed reducing the frequency of local recurrence in 2 times from 16.7% to 8.3% and increasing a 3-year overall survival by 10%--from 63% to 73%, which shows intraoperative intrapelvic chemotherapy with hyperthermia as an effective method in the prevention of local recurrences.
Experience of treatment of 14 patients with cancer recti, using chemoradiation impact on the tumor--endolymphatic polychemotherapy according to MFP (metotrexat, fluorouracyl cysplatin) schema and intense irradiation (summary focal dose 25 Gr) on the first stage with subsequent performance of surgical intervention in terms before 24 hours after completion of irradiation. The immediate results of treatment are estimated. There was not revealed the postoperative complications frequency enhancement. The anal sphincter function restoration was observed at the same terms as after performance of conventional surgical treatment.