Postoperative Chemotherapy In Patients Research Articles

Nursing about postoperative chemotherapy for patients with cervical carcinoma

化疗药物对正常组织具有严重的毒性和刺激性,给患者造成痛苦,导致患者中途放弃治疗.为了提高宫颈癌患者生存质量,减少化疗期间的不良反应,使患者顺利完成化疗.现回顾2006年3月至2009年3月我院收治的56例宫颈癌术后化疗患者的护理资料,现报道如下。

Preoperative versus Postoperative Chemotherapy in Patients with Resectable Non-small Cell Lung Cancer: Systematic Review and Indirect Comparison Meta-Analysis of Randomized Trials

A large number of trials have evaluated the efficacy of postoperative chemotherapy on survival after resection for lung cancer, and a smaller number have evaluated preoperative chemotherapy on survival for potentially resectable lung cancer, but no direct comparison has yet been published comparing the two approaches. We conducted a systematic review of randomized trials, extracted time-to-event data using Parmar methods (when not reported), used random effects meta-analysis to evaluate overall and disease survival treatment effects and performed indirect comparison meta-analysis to obtain the relative hazards of postoperative to preoperative administration on survival. Data were abstracted from 32 randomized trials involving more than 10,000 participants, with 22 trials administering postoperative and 10 trials administering preoperative chemotherapy. For overall survival, the hazard ratios were 0.80 (0.74-0.87; p < 0.001) and 0.81 (0.68-0.97; p = 0.024) in postoperative chemotherapy group and preoperative chemotherapy group, respectively. Using indirect comparison meta-analysis, the relative hazards of postoperative compared with preoperative administration was 0.99 (0.81-1.21; p = 0.91). For disease-free survival, the hazard ratios were 0.76 (0.67-0.86; p < 0.001) and 0.79 (0.63 to 1.00; P = 0.050) in postoperative chemotherapy group and preoperative chemotherapy group, respectively. Using indirect comparison meta-analysis, the relative hazards of postoperative compared with preoperative administration was 0.96 (0.77-1.20; p = 0.70). In patients with resectable lung cancer, there was no evidence of a difference in overall and disease-free survival between the timing of administration of chemotherapy (postoperative versus preoperative).

Effects of Expression of ERCC1, RRM1 on Survival Trend of Lung Cancer with Cisplatin Combine Gemcitabine Chemotherapy after Surgical Resection.

It has been proved that the chemotherapy respouse was related to the expression levels of tumor genes in lung cancer. The aim of this study was to explor the relationship of ERCC1, RRM1 expression and the benefits from postoperative cisplatin combined with gemcitabine (GP) chemotherapy in patients with non-small cell lung cancer (NSCLC). All 57 postoperative patients with stage II-IV NSCLC were entered into the study, and 39 cases of patients were at least received 2 cycles of cisplatin combind with gemcitabine chemotherapy, 18 cases with no chemotherapy. Immunohistochemistry was performed in paraffin-embedded tumor specimens to investigate ERCC1, RRM1 expression. Cox proportional regression analysis was used to screen independent prognostic risk factors for survival. Comparisons of the median survival time among groups were based on Kaplan-Meier analysis. Cox regression analyses showed that the extent of tumor resection, chemotherapy after surgical resection and expressions of ERCC1 were independent prognostic factors. In the group of high expression of ERCC1, the median survival time of postoperative chemotherapy patients and control were 42 and 12 months respectively (P =0.018). In the group with low expression of ERCC1, the median survival time of postoperative chemotherapy patients and control were 23 and 21 months respectively (P =0.088). However, In the group of high expression of RRM1, the median survival time of postoperative chemotherapy patients and control were 28 and 21 months respectively (P =0.092). In the group with low expression of RRM1, the median survival time of postoperative chemotherapy patients and control were 42 and 22 months respectively (P =0.010). The NSCLC patients with high expression of ERCC1 and low expression of RRM1 get more probablely benefits from postoperative cisplatin combine gemcitabine chemotherapy.

Factors Related to Recurrence after Pathological Complete Response to Postoperative Chemotherapy in Patients with Epithelial Ovarian Cancer

It has been appreciated for some time that the lack of detection of ovarian cancer at clinical and pathological (second-look laparotomy) evaluation is not synonymous with cure. The goal of this study was to define clinical risk factors for recurrence after complete pathological response to postoperative chemotherapy in patients with epithelial ovarian cancer. Fifty-seven patients who met the inclusion criteria of our study were evaluated. The characteristics (age, menopausal status, histological subtype, tumor grade, presence of ascites at diagnosis, type of omentectomy, FIGO stage, and residual tumor volume after primary surgery) of patients with and those without tumor recurrence were compared. The median follow-up was 52 months (range, 15-142 months). The overall survival rates of the patients were 100%, 96%, and 87% at 1, 3 and 5 years, respectively. At the time of the study analysis, 21 of 57 (37%) patients had recurrent disease. The median time to recurrence was 16 months. Recurrences were most frequent in the pelvis and abdominal cavity (38%). Age, menopausal status, stage at diagnosis, and residual tumor volume after initial surgery were significantly related to the risk of recurrence in univariate analysis (P = 0.039, 0.038, 0.004, and 0.000, respectively). Residual tumor volume after initial surgery was found to be the only significant independent prognostic factor (P = 0.049, HR: 0.16, 95% CI: 0.02-0.99). We believe it is necessary to conduct randomized studies on this issue because insight into predictors of recurrence after pathological complete response to postoperative chemotherapy could be used to select patients for trials of consolidation therapy.

Oral Uracil and Tegafur Compared With Classic Cyclophosphamide, Methotrexate, Fluorouracil As Postoperative Chemotherapy in Patients With Node-Negative, High-Risk Breast Cancer: National Surgical Adjuvant Study for Breast Cancer 01 Trial

The primary aim of this study was to compare the effectiveness of oral uracil-tegafur (UFT) with that of classical cyclophosphamide, methotrexate, and fluorouracil (CMF) given as postoperative adjuvant treatment to women with node-negative, high-risk breast cancer. Women with node-negative, high-risk breast cancer were randomly assigned to receive either 2 years of UFT or six cycles of CMF after surgery. The primary end point was relapse-free survival (RFS). Overall survival (OS), toxicity, and quality of life (QOL) were secondary end points. The hypothesis was that UFT was not inferior to CMF in terms of RFS. Between October 1996 and April 2001, a total of 733 patients were randomly assigned to receive either treatment. The median follow-up time was 6.2 years. The RFS rates at 5 years were 88.0% in the CMF arm and 87.8% in the UFT arm. OS rates were 96.0% and 96.2%, respectively. The hazard ratios of the UFT arm relative to the CMF arm were 0.98 for RFS (95% CI, 0.66 to 1.45; P = .92) and 0.81 for OS (95% CI, 0.44 to 1.48; P = .49). The toxicity profiles differed between the two groups. The QOL scores were better for patients given UFT than those given CMF. RFS and OS with oral UFT were similar to those with classical CMF. Given the higher QOL scores, oral UFT is a promising alternative to CMF for postoperative adjuvant chemotherapy in women with node-negative, high-risk breast cancer.

Expression of CK20 mRNA in the peripheral blood around postoperative chemotherapy in patients with gastric cancer and its clinical significance

To investigate whether CK20 mRNA expression level could be considered as an effective molecular indicator for evaluation of chemotherapy sensitivity. All samples of peripheral blood were taken from 31 gastric cancer patients undergone radical operation a week before postoperative chemotherapy, at the first day of chemotherapy point, and after the first cycle of chemotherapy respectively, and subjected to FQ RT-PCR assay for CK20 mRNA. The chemotherapy scheme was FOLFOX 4. The control group was 15 healthy volunteers. Aomng the 31 gastric cancer patients, the value of CK20 mRNA before postoperative chemotherapy was increased (2.96+/-2.27 vs 2.22+/-2.12, t=2.10, P<0.05) in 25 positive cases, and then declined after chemotherapy(2.05+/-1.86 vs 2.96+/-2.27, t=2.50, P<0.05) in 24 positive cases. The expression level of CK20 mRNA in patients before chemotherapy was increased in 16 cases(51.6%), declined in 9 cases(29.0%) and stabilized as negative in 6 cases(19.4%). After chemotherapy the level of CK20 mRNA was increased in 7 cases(22.6%), declined in 17 cases (54.8%) and stabilized as negative in 7 cases(22.6%), there was significant difference between the two groups(chi(2)=6.06, P<0.05). The expression level of CK20 mRNA in the peripheral blood detected by FQ RT-PCR in patients with gastric cancer declines after postoperative adjuvant chemotherapy. Different individuals have different sensitivity to chemotherapeutics. Dynamic monitoring CK20 mRNA should be considered as an effective index to evaluate the efficacy of postoperative adjuvant chemotherapy.

Annexin II Overexpression Predicts Rapid Recurrence after Surgery in Pancreatic Cancer Patients Undergoing Gemcitabine-Adjuvant Chemotherapy

Gemcitabine has been shown to exhibit significant clinical activity against pancreatic cancer and has become a first-line chemotherapeutic for this disease in recent years. However, there are still many patients who do not respond to this treatment and it is expected to improve the clinical outcome if we can develop a method to predict the efficacy of gemcitabine before treatment. The purpose of this study was to determine novel factors that make pancreatic cancer resistant to gemcitabine. Using the high-resolution proteomic approach, agarose two-dimensional gel electrophoresis, we compared protein profiling of a gemcitabine-resistant pancreatic cancer cell line with its wild-type. We identified Annexin II as an up-regulated protein in the gemcitabine-resistant pancreatic cancer cell line. Immunohistochemistry demonstrated that Annexin II was mainly expressed at the cell surface of pancreatic cancer cells. Interestingly, Annexin II overexpression in cancer cells was significantly associated with rapid recurrence after gemcitabine adjuvant chemotherapy in postoperative patients (P = .0078), and its staining was also an independent prognostic indicator of recurrence in pancreatic cancer patients who underwent adjuvant gemcitabine treatment after curative surgery on multivariate analysis (P = .0047). In addition, inhibition of Annexin II expression by siRNA in pancreatic cancer cell lines increased the cytotoxic efficacy of gemcitabine. These results indicate that Annexin II overexpression may induce gemcitabine resistance in pancreatic cancer resulting in rapid recurrence. Analysis of Annexin II expression in cancer tissues may predict the clinical outcome of gemcitabine treatment, leading to the development of a new method for tailor-made treatment for this disease.

Survival after recurrent osteosarcoma: Data from three European Osteosarcoma Intergroup (EOI) randomized controlled

10505 Background: Between 1983 and 2002, the EOI accrued to three randomized controlled trials of pre- and postoperative chemotherapy for patients (pts) with resectable nonmetastatic high-grade osteosarcoma of the extremity: MRC-BO02, BO03 and BO06 (also known as EORTC-80831, 80861 and 80931) with n=179, 391 and 497 pts randomised, respectively. Control treatment in all trials was doxorubicin 75 mg/m2 + cisplatin 100 mg/m2 (DC). The comparators were additional high-dose methotrexate (BO02), T10-based multi- drug regimen (BO03) and G-CSF intensified-DC (BO06). No statistically significant differences between treatments were reported in the original trial reports. Methods: Survival after recurrence was investigated with standard survival analysis methods, including all 1,067 pts from the 3 trials. Results: Median recurrence-free survival was 31 months (m); only 4 recurrences were reported later than 5 years. In 564 pts with recurrence (median 13m post-randomisation), there was no difference in 5-year survival between first-line treatment arms (13–19%). Pts with good histologic response to preoperative chemotherapy had better overall survival after recurrence than poor responders (p=0.015). Pts whose disease recurred within 2 years after randomization had worse prognosis than those recurring after 2 years (14 vs 35% at 5 years; p<0.001). Local relapse was more often reported after limb saving procedures (5 vs 25%), independent of the primary tumor site. Site of first recurrence (in total: local 20%, lung 62%, other 18%) affected survival as pts recurring with metastases other than lung had significantly worse overall survival (local 27%, lung 18%, other 10% at 5 years, p=0.001). Conclusions: These data describe the largest series of pts with recurrent osteosarcoma. They confirm the relationship between early recurrence and poor survival. New findings include worse survival in pts with a recurrence after poor histologic response to preoperative chemotherapy. No significant financial relationships to disclose.

Preoperative versus postoperative chemotherapy in patients with resectable non-small cell lung cancer: Systematic review and indirect comparison meta-analysis of randomized trials

7546 Background: A large number of trials evaluated the efficacy of postoperative chemotherapy after resection for lung cancer. A smaller number evaluated preoperative chemotherapy for potentially resectable lung cancer, but no direct comparison has yet been published comparing the two approaches. Methods: We conducted a systematic review of randomized trials, extracted time-to-event data using Parmar methods (when not reported), used random effects meta-analysis to evaluate overall and disease survival treatment effects and performed indirect comparison using surgery (without chemotherapy) as the common comparison. Results: 112 publications were identified and 56 potentially relevant trials retrieved for more detailed evaluation. In total, 17 were excluded for repeat data and data from 8 studies could not be extracted for meta-analysis, leaving 31 randomized trials involving over 10,000 participants, with 21 trials administering postoperative and 10 trials administering preoperative chemotherapy. For ove...

Preoperative chemotherapy is safe in early breast cancer, even after 10 years of follow-up; clinical and translational results from the EORTC trial 10902

The Preoperative Chemotherapy in Primary Operable Breast Cancer (POCOB) study was designed to compare preoperative with postoperative chemotherapy in patients with early breast cancer concerning breast conserving therapy (BCT) procedures, disease free survival (DFS) and overall survival (OS). Patients (n = 698) with early breast cancer were enrolled between 1991 and 1999 and randomized between preoperative versus postoperative chemotherapy (four cycles of fluorouracil, epirubicin, and cyclophosphamide). Endpoints were BCT procedures, DFS, OS, and tumor response to preoperative chemotherapy. In addition, tumor tissue was collected for translational research and the following markers were examined: ER, PgR, HER2, p21, p53, and bcl-2 expression. With a median follow-up of 10 years, there was no statistically significant difference between the two treatment arms for OS (HR = 1.09; 95%CI 0.83-1.42; P = 0.54), DFS (HR = 1.12; 95%CI 0.90-1.39; P = 0.30), or locoregional recurrences (LRR, HR = 1.16; 95%CI 0.77-1.74). Preoperative chemotherapy was associated with an increase in BCT rates. BCT in part feasible due to tumor downsizing after preoperative chemotherapy was not correlated with higher LRR or worse OS compared to BCT which was feasible without downsizing of the tumor. Using available tumor material, only tumor stage, nodal stage, and grade were independent prognostic factors for overall survival. Preoperative chemotherapy does not result in a difference in OS or DFS compared to postoperative chemotherapy in patients with early breast cancer. Moreover, it increases BCT rates with no significant increase of LRR. This implies that preoperative chemotherapy is a safe procedure for patients with early breast cancer, even after a follow-up period of 10 years.

Preoperative versus postoperative chemotherapy for patients undergoing resection for lung cancer. Systematic review and indirect comparison meta-analysis of randomised trials

Preoperative versus postoperative chemotherapy for patients undergoing resection for lung cancer. Systematic review and indirect comparison meta-analysis of randomised trials

Oral uracil-tegafur (UFT) compared to classical cyclophosphamide/methotrexate/5-fluorouracil (CMF) as postoperative chemotherapy in patients with node-negative, high-risk breast cancer (BC): Results of the national surgical adjuvant study for breast cancer

551 Background: Oral UFT and classical (c-) CMF provide similar response rates in patients (pts) with metastatic BC (CMF: 36.1%, UFT: 39.3%). In a postoperative setting, these regimens showed comparable effectiveness in terms of odds reductions in relapse-free survival (RFS) (CMF: 23.5%, UFT: 21.0%), but data fromrandomized controlled trials (RCT) is not sufficient. Methods: We conducted a RCT to study the efficacy and toxicity of 2-year oral UFT as compared with c-CMF in pts with Stage I - IIIA node-negative, pathologically high-risk BC in a postoperative setting. In the CMF arm, pts received 6 cycles of c-CMF (C: 100 mg po, days 1 to 14, M: 40 mg/m2 iv, days 1 and 8, F: 500 mg/m2 iv, days 1 and 8). In the UFT arm, pts received UFT at 300 mg/m2/day po for 2 years. Tamoxifen (20 mg/day) was administered for 5 years if ER or PgR was positive or unknown. The primary endpoint was RFS. Overall survival (OS), toxicity, and quality of life were secondary endpoints. The statistical hypothesis was non- inferiority of UFT in terms of RFS (95% CI of HR: &lt;1.30). Results: From October 1996 through March 2001, a total of 733 pts were enrolled of whom 707 pts were analyzed. Patients’ characteristics were well balanced between the two arms. Median follow-up time was 6.1 years. At 5 years the RFS rate was 88.2% in the CMF arm and 87.7% in the UFT arm, and OS rates were 96.0% and 96.1%, respectively. Hazard ratios of the UFT arm to the CMF arm were 1.05 (95% CI: 0.69–1.57) for RFS and 0.88 (95% CI: 0.48–1.63) for OS. The toxicity profile differed between the groups. Major grade 3 or higher adverse events were as follows: leukopenia (CMF: 3.1%, UFT: 0.3%, p=0.006), neutropenia (CMF: 5.5%, UFT: 3.5%, p=0.27), elevation of total bilirubin (CMF: 0.3%, UFT: 5.5%, p=0.00001), elevation of GOT (CMF: 1.4%, UFT: 5.7%, p=0.004), elevation of GPT (CMF: 5.1%, UFT: 8.9%, p=0.08), nausea/vomiting (CMF: 2.8%, UFT: 1.1%, p=0.18) and diarrhea, (CMF: 0.3%, UFT: 2.0%, p=0.04). Conclusions: Our results suggest that UFT is a promising alternative to CMF as postoperative adjuvant chemotherapy in women with node-negative, high-risk breast cancer. No significant financial relationships to disclose.

Evidence-Based Recommendations for Local Therapy for Soft Tissue Sarcomas

There has been a gradual migration in the local treatment of soft tissue sarcomas from amputation and similar radical resectional approaches to more conservative, function-preserving surgery combined with radiotherapy. This progress has been made possible by small, single-institution, randomized trials that demonstrated the superiority of this more conservative, combined-modality approach. In the new millennium, attention has shifted to defining subsets of patients who might be adequately treated by surgery alone and defining the optimal sequence of surgery and radiation for patients who require both types of local therapy. There remains considerable discussion and debate surrounding the issue of pre- and postoperative chemotherapy for patients with localized soft tissue sarcomas. Adjuvant chemotherapy is a standard of care for adults who have the subtypes of soft tissue sarcomas that typically occur in pediatric patients (Ewing sarcoma, rhabdomyosarcoma), and just as clearly, adjuvant chemotherapy is not warranted in patients with low- and intermediate-risk disease (stages I and II). For patients with higher risk disease (stage III), the available randomized trials do not convincingly demonstrate a clinical benefit to adjuvant chemotherapy. As such, a complete accounting of potential risks and benefits is appropriate when discussing adjuvant chemotherapy with patients who have stage III disease.

Tumor response to pre-operative chemotherapy (CT) with FOLFOX-4 for resectable colorectal cancer liver metastases (LM). Interim results of EORTC Intergroup randomized phase III study 40983

3500 Background: After resection of LM, 5y survival is 30%, but cancer recurrence is frequent. The benefit of combining surgery and CT has not yet formally been proven. Methods: This study evaluates the value of pre- and postoperative CT in patients with potentially resectable liver metastases from colorectal cancer. Between September 2000 and July 2004, 364 patients were randomized between peri-operative FOLFOX4 (oxaliplatin 85mg/m2 and LV5FU2), 6 cycles before and 6 cycles after surgery (182 patients), and surgery alone (182 patients). The primary endpoint was progression free survival. The purpose of this analysis was to evaluate tumor response to pre-operative treatment and determine if CT induces a tumor size reduction. Results: Baseline characteristics were similar in both arms: median age: 62.5 yrs, prior adjuvant CT: 41.8%, 1 to 3 metastases: 92.3%, T3 or T4: 80.8%. In the CT arm, 97.7% of the patients were documented to have completed pre-operative CT (81.5% received 6 preoperative cycles). 28.9% of the patients who started pre-operative CT required a dose reduction. Of all patients entered in the trial, 88.3% and 94.9% underwent surgery in the CT and surgery arms, respectively. Resection was achieved in 95.6% of the patients operated (84.4% of all patients) in the CT arm, and 89.2% of the patients operated (84.7% of all patients) in the surgery arm. As previously reported, preoperative chemotherapy was safely administered. From imaging data (CT scan), median sum of largest diameters of lesions was 45 mm [Q1-Q3:28.0–70.0] (both arms) before treatment and decreased to 30 mm [Q1-Q3: 15.0–55.0] after CT (median relative difference of 29.7%). At pathological examination, median sum of largest diameters of lesions was 34.5 mm [Q1-Q3:20.0–53.0] in the CT arm and 45 mm [Q1-Q3: 29.0–69.0] in the surgery arm. Conclusions: CT scan measurements were consistent with those performed at pathological examination. Pre-operative CT with 6 cycles of FOLFOX4 resulted in a decrease in diameter of lesions. Since size of metastases at time of surgery is known to have an impact on survival, it is possible that preoperative chemotherapy will improve survival. Survival data should be available at the end of 2006. No significant financial relationships to disclose.

Reduction of postoperative chemotherapy in children with stage I intermediate-risk and anaplastic Wilms' tumour (SIOP 93-01 trial): a randomised controlled trial

Present treatment for Wilms' tumour is very successful. Now, efforts are aimed at reducing toxicity and burden of treatment by shortening schedules without loss of effectiveness. The objective of this randomised trial was to assess whether postoperative chemotherapy for patients with stage I intermediate-risk and anaplastic Wilms' tumour could be shortened to only 4 weeks from the standard 18 weeks, while maintaining equivalent event-free survival. Between June, 1993, and June, 2000, 410 patients were randomly assigned after four doses of vincristine plus one course of dactinomycin postoperatively either to stop further adjuvant chemotherapy (no further chemotherapy group, n=200), or to receive a further two courses of the same chemotherapy (standard group, n=210). Previous treatment consisted of chemotherapy before nephrectomy of four doses of vincristine and two courses of dactinomycin followed by surgical resection of the tumour. Eligible patients were at least 6 months old and had stage I tumours with either intermediate-risk histology or anaplasia. The primary endpoint of this equivalence trial was 2-year event-free survival. Both per-protocol and intention-to-treat analyses were done. By 2 years, 18 recurrences were reported in the standard group, and 22 in the no further chemotherapy group. Event-free survival was 91.4% (95% CI 87.5-95.2) for the no further chemotherapy group and 88.8% (84.3-93.2) for the standard group (difference=2.6%, upper 97.5% confidence limit 8.4%). The null hypothesis, that experimental treatment is less effective than standard treatment, could be rejected (p=0.008). Shortening duration of chemotherapy could reduce acute and late side-effects and inconvenience for patient and parents while maintaining effectiveness, and could be beneficial in terms of health costs.

Metastatic neuroendocrine tumors of the parotid gland

Objectives To present 2 cases of neuroendocrine tumors of the parotid gland and to review the clinical presentation, histopathologic, and immunohistochemical findings and treatment of these rare tumors. Study design Case series. Methods This study reviews 2 patients who both presented with firm masses in the parotid gland diagnosed as neuroendocrine carcinoma by histopathologic and immunohistochemical examination. The evaluation, diagnosis, and treatment are discussed. Results Both patients underwent complete tumor extirpation via a total or subtotal parotidectomy. Both patients received postoperative radiation therapy and chemotherapy. Conclusions Neuroendocrine tumors of the parotid gland are uncommon lesions; however, they have a favorable prognosis as compared to their pulmonary counterparts with early diagnosis and aggressive treatment. Diagnosis is based on the immunohistochemical characteristics of the tumor. Appropriate treatment includes complete surgical excision with postoperative radiation therapy to the parotid bed with the addition of postoperative chemotherapy in patients suspected to have metastatic disease.

Effect of difluoromethylornithine, a chemotherapeutic agent, on wound healing

Introduction: Difluoromethylornithine (DFMO) is a potential chemotherapeutic agent and currently in Phase II trials for colon and prostate malignancies. DFMO will potentially be used for chemotherapy in postoperative patients in low dosage. Therefore, we studied the effect of low dosage DFMO on wound healing. Methods: Two groups of twenty male Sprague Dawley rats underwent a midline dorsal incision with implantation of polyvinyl alcohol sponges into subcutaneous pockets. In Exp 1, ten rats were injected daily with DMFO (500 mg/kg IP) starting on day of wounding while controls (ten rats) received equivalent volume of normal saline. In Exp 2, DFMO and normal saline treatments were delayed until post-wounding day 3. All rats were sacrificed on day 10 post-wounding. Incisional wound breaking strength (WBS, g) and sponge hydroxyproline (OHP, g/100mg sponge) content (collagen deposition), were assessed. Efficacy of DFMO treatment was assessed by measuring wound fluid polyamines, putrescine (PUT) and spermidine (SPER)(M) Results: Treatment with DFMO starting on day 0 (Exp 1) resulted in a significant decrease in collagen deposition and wound breaking strength. Neither of the wound healing parameters was affected when treatment was begun 3 days post-wounding (Exp 2). Conclusion: Wound healing is decreased when DFMO treatment is started on the day of surgery. This suggests that DFMO treatment may play a critical role in the synthesis of collagen in early wound healing and chemotherapy with DFMO should be delayed for patients requiring surgery. TABLE—ABSTRACT P116GroupWBSOHPPUTSPEREXP 1Control409 ± 821435 ± 10211.6 ± 3.4NDDFMO340 ± 41∗1014 ± 67∗∗2.2 ± 0.4∗∗NDEXP 2Control376 ± 941568 ± 9015.3 ± 5.295.4 ± 18.6DFMO354 ± 411624 ± 1505.7 ± 5.4∗∗63.1 ± 12.8∗∗Mean ± standard deviation.∗P < 0.05 and∗∗P < 0.005 by t-test; Student’s t-test; ND—not determined.

Molecular lesions in colorectal cancer: impact on prognosis? Original data and review of the literature.

In the Dukes' B and C stages of colorectal carcinoma there are considerable variations in the observed courses of the disease. Since post-operative chemotherapy in patients with Dukes' C (node-positive) colon carcinoma has been demonstrated to be effective in improving overall-survival, a more exact prognosis assessment gains additional significance and therapeutic relevance. One also hopes to derive improved prognostic factors from the clarification of the molecular pathogenesis. Because of its frequency and the accessibility and recognizability of its developmental stages colorectal carcinoma is among the best investigated of all solid tumors. Despite a multitude of suggested molecular candidate markers none of these changes has yet been able enter the everyday life of the clinic. However, it is to be expected that some of the molecular alterations presently discussed will gain importance before long in the clinical treatment of patients with colorectal carcinoma. Considering also our own findings, this review presents the latest developments in the scientific discussion of the tumor suppressor/oncogenes p53, k-ras, and DCC, biochemical determinants of the 5-fluorouracil metabolism, and defects of the DNA repair system.

Primary systemic therapy of carcinoma of the breast - update of the geparduo studies

Primary systemic therapy represents today the standard of care in patients with locally advanced breast cancer and becomes more and more an alternative to adjuvant postoperative chemotherapy in patients with operable breast cancer. In a subset of large randomized trials it could be shown that sequential schedules with more than 4 cycles can reach the highest rates of clinical and histopathological complete remissions. In two randomized trials (NSABP B-27, Geparduo) using 4 cycles of Adriamycin/Cyclophosphamide followed by 4 cycles of Docetaxel significant better results could be obtained in comparison with the referring control arm. New approaches try to further individualize chemotherapy, either using molecular biological tumor factors or the early effect of some chemotherapy cycles. In the Gepartrio study clinical response evaluation after 2 cycles can identify patients with a high or low chance for a histopathological complete remission and further treatment strategies can be developed for these different subgroups.

Postoperative chemotherapy in advanced ovarian granulosa cell tumors

The objective of this research is to assess the use of first-line postoperative chemotherapy in patients with advanced ovarian granulosa cell tumor (GCT). A retrospective population-based case series identified 60 women with stage IC or greater ovarian GCT over a 25-year period. Five patients were excluded because of incomplete information. None of the patients had received chemotherapy or radiotherapy prior to the diagnosis of advanced GCT. All patients had, at a minimum, a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pathology was centrally reviewed and the diagnosis confirmed. Of the 55 eligible patients, the 21 women with stage III and IV disease were the main focus of the study. Clinical outcomes and survival were compared between 13 women who received combination chemotherapy and eight who did not. Univariate analysis was conducted to assess the impact of age at diagnosis, size of residual disease, and adjuvant use of radiation therapy on prognosis. For the 55 patients, median age at diagnosis was 54 years (range 22-79). Median length of follow-up was 4.4 years (range 0.3-23.3). Median time to progression was 2.3 years (range 0.3-5.3). Sixty percent of those with no macroscopic disease after primary surgery recurred within 4.5 years of diagnosis. All patients with gross residual disease (>2 cm) were dead within 4 years of diagnosis. Overall 5 years survival rate was 61.6% (95% CI (49.3-76.9)). Among stage III and IV patients, there were no differences with respect to age at diagnosis and use of radiation therapy between those who did and did not receive chemotherapy. The only statistically significant difference was the presence of macroscopic residual disease (82% vs. 22%). Although there was no statistical significant difference in overall survival, there was a trend toward a poorer outcome in the group that received chemotherapy. Survival of patients with macroscopic residual disease was not influenced by use of chemotherapy (P = 0.976). We conclude that the presence of macroscopic residual disease after primary surgery was the most important prognostic factor. Although these patients were more likely to receive postoperative chemotherapy, there was no evidence to document a beneficial effect of systemic therapy in this group of women.