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Results for “pathologic complete response”

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PubMed2001

Analysis of treatment failures and survival of patients with fallopian tube carcinoma: a cooperation task force (CTF) study.

OBJECTIVE: The objective of this retrospective multicenter study was to assess the pattern of failures and survival of patients with primary carcinoma of the fallopian tube. METHODS: The hospital records of 88 patients with primary carcinoma of the fallopian tube were reviewed. Surgery was the initial therapy for all patients. Tumor stage was I in 21 (23.9%), II in 21 (23.9%), III in 43 (48.8%), and IV in 3 (3.4%) patients. Postoperative treatment was given without well-defined protocols. The median follow-up of survivors was 55 months (range, 7-182). RESULTS: Of the 21 patients with stage I disease, 10 had no postoperative treatment and 11 had platinum-based chemotherapy. Five (23.8%) patients recurred after a median of 29 months (range, 8-93) from initial surgery. Of the 21 patients with stage II disease, 2 had no postoperative treatment, 2 underwent external pelvic irradiation, 16 received platinum-based chemotherapy, and 1 patient had oral melphalan. Eight (38.1%) patients recurred after a median of 25.5 months (range, 7-57). Of the 46 patients with stage III-IV disease, 1 patient refused chemotherapy and died after 19 months and 45 patients received platinum-based chemotherapy. A clinical complete response was obtained in 29 (64.4%) patients and a partial response in 8 (17.8%). A second-look laparotomy was performed in 14 of the 29 clinically complete responders: 12 patients were found to be in pathological complete response and 2 had persistent disease. Six (50.0%) of the former recurred after a median of 22 months (range, 13-101) from initial surgery. The two patients with persistent disease developed tumor progression after 15 and 11 months, respectively. Fifteen clinically complete responders did not undergo second-look, and 7 (46.7%) of them had a recurrence after a median of 18 months (range, 9-41). For the whole series, 5-year survival was 57%. By log-rank test, survival was related to FIGO stage (III-IV vs I-II, P = 0.0001), tumor grade (G3 vs G1 + G2, P = 0.0038), and patient age (>58.5 years vs <58.5 years, P = 0.0069), but not to histological type. The Cox model showed that FIGO stage (P = 0.0018) and patient age (P = 0.0290) were independent prognostic variables for survival. Among the patients with stage III-IV disease, 5-year survival was 55% for the patients who had residual tumor <1 cm compared with 21% for those who had larger residuum (P = 0.0169). CONCLUSIONS: Primary carcinoma of the fallopian tube shares several biological and clinical features with ovarian carcinoma. However, when compared with the latter, fallopian tube carcinoma more often tends to recur in retroperitoneal nodes and distant sites. Stage, patient age, and, among patients with advanced disease, residual tumor after initial surgery represent important prognostic variables for survival.

Adult↗
PubMed2006

Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer.

PURPOSE: To evaluate neoadjuvant capecitabine/oxaliplatin before chemoradiotherapy (CRT) and total mesorectal excision (TME) in newly diagnosed patients with magnetic resonance imaging (MRI) -defined poor-risk rectal cancer. PATIENTS AND METHODS: MRI criteria for poor-risk rectal cancer were tumors within 1 mm of mesorectal fascia (ie, circumferential resection margin threatened), T3 tumors at or below levators, tumors extending > or = 5 mm into perirectal fat, T4 tumors, and T1-4N2 tumors. Patients received 12 weeks of neoadjuvant capecitabine/oxaliplatin followed by concomitant capecitabine and radiotherapy. TME was planned 6 weeks after CRT. Postoperatively, patients received another 12 weeks of capecitabine. RESULTS: Between November 2001 and August 2004, 77 eligible patients were recruited. After neoadjuvant capecitabine/oxaliplatin, the radiologic response rate was 88%. In addition, 86% of patients had symptomatic responses in a median of 32 days (ie, just over one cycle of capecitabine/oxaliplatin). After CRT, the tumor response rate was increased to 97%. Three patients remained inoperable. Sixty-seven patients proceeded to TME, and all but one patient had R0 resection. Pathologic complete response was observed in 16 patients (24%; 95% CI, 14% to 36%), and in an additional 32 patients (48%), only microscopic tumor foci were found on surgical specimens. Four deaths occurred during neoadjuvant capecitabine/oxaliplatin therapy as a result of pulmonary embolism, ischemic heart disease, sudden death with history of chest pain, and neutropenic colitis. CONCLUSION: Capecitabine/oxaliplatin before synchronous CRT and TME results in substantial tumor regression, rapid symptomatic response, and achievement of R0 resection.

Adult↗
PubMed2000

[A case of neuroendocrine tumor of the urinary bladder].

We present a case of a neuroendocrine tumor of the urinary bladder. A 81-year-old-man presented with macrohematuria and difficult voiding. Cystoscopy, computed tomography (CT) and magnetic resonance imaging (MRI) revealed non-papillary broad-based bladder tumor, benign prostatic hyperplasia and three bladder stones. Histological diagnosis was neuroendocrine tumor of the urinary bladder and he underwent two courses of trans-arterial infusion (neoadjuvant) chemotherapy. After two courses of chemotherapy, pelvic CT scan revealed partial response and then the patient underwent transurethral resection of the bladder tumor, simultaneously with TUR-P and cystolithotripsy. Examination of the resected specimen indicated pathological complete remission and he discharged. Although the patient was followed-up postoperatively because of pathological complete response, the tumor recurred in the bladder three months later.

Aged↗
PubMed2003

Epidermal growth factor receptor, p53 mutation, and pathological response predict survival in patients with locally advanced esophageal cancer treated with preoperative chemoradiotherapy.

PURPOSE: Despite the availability of cellular markers associated with cell cycle, apoptosis, and DNA repair, predictive factors for pathological complete response (CR) and overall survival (OS) are few in patients with locally advanced esophageal cancer. This study evaluates the role of clinical and cellular markers in predicting CR and OS in patients with esophageal cancer. EXPERIMENTAL DESIGN: Patients were treated with infusional cisplatin and 5-fluorouracil combined with daily radiotherapy followed by esophagectomy. Pretreatment tumors (n = 54) were analyzed for epidermal growth factor receptor (EGF-R), bax, and bcl-2 expression by immunohistochemistry and for p53 mutations by direct DNA sequencing of exons 5-8. Clinical covariates included patients' age at enrollment; gender; Barrett's metaplasia; and tumor location, histology, and differentiation. Logistic regression and survival analyses were used to evaluate the predictors. RESULTS: Age ranged from 32 to 75 years; most patients were male (45 male; 9 female); and tumors were distal (47 distal; 7 mid), adenocarcinoma (41 adenocarcinomas; 13 squamous cell carcinomas), and moderately differentiated (33 moderate; 6 well; 15 poor). Female gender predicted CR (odds ratio 7.5; 95% confidence interval, 1.4-41). The OS was 43% at 5 years. Presence of CR (P < 0.001 log rank) and p53 mutation (P = 0.051 log rank) correlated with increased OS, whereas increased EGF-R expression predicted poor OS (P = 0.009 log rank). EGF-R remained significant when adjusted for clinical covariates. There was a trend toward increased OS related to better tumor differentiation and decreased bcl-2. CONCLUSIONS: These data suggest that EGF-R and p53 mutation may be used as both outcome predictors and targets for molecular therapy for esophageal cancer.

Adenocarcinoma↗
PubMedDate not supplied

Comparative study of chemoradiation and neoadjuvant chemotherapy effects before radical hysterectomy in stage IB-IIB bulky cervical cancer and with tumor diameter greater than 4 cm.

Tumor size seems to be a determinant in the prognosis of early cervical cancer. Patients with tumor greater than 4 cm (bulky) in diameter have worse outcome. The purpose of this study was to compare the efficacy of preoperative combined chemoradiation and neoadjuvant chemotherapy (NAIC) programs followed by radical hysterectomy in stage IB-IIB bulky cervical cancer. From September 1999 to April 2002, 60 patients with stage IB-IIB bulky cervical cancer were treated with preoperative external-beam radiotherapy to 45 Gy plus weekly cisplatin 50 mg/m2 or preoperative NAIC by cisplatin 50 mg/m2 and vincristin 1 mg/m2 every 7-10 days, for three courses. Surgery was performed 4-6 weeks after the completion of the preoperative treatment. There were no significant difference between age, stage, tumor size, and histopathologic type in two groups (P > 0.05). Toxicity associated with two treatment methods was usually mild. In chemoradiation group, two patients developed vesicovaginal fistula, and four patients developed long-term hydronephrosis that needed urethral stenting. Before surgery, complete and partial clinical response had no significant difference between two groups (P > 0.05). After surgery, lymph node and parametrial involvement had no significant difference between two groups (P > 0.05). In NAIC group, more patients had significantly residual tumor (P = 0.012), but residual tumor size had no significant difference between two groups (P > 0.05). Pathologic complete response was significantly higher in chemoradiation group (P = 0.004). According to the result of this study, it seems that NAIC and chemoradiation had similar effects in survival prognostic factors.

Adult↗
PubMed1998

High dose chemoradiotherapy followed by esophagectomy for adenocarcinoma of the esophagus and gastroesophageal junction: results of a phase II study of the Eastern Cooperative Oncology Group.

BACKGROUND: To assess the toxicity, local response, and survival associated with multimodality therapy in a cooperative group setting, patients with biopsy-proven clinical Stage I or II adenocarcinoma of the esophagus (staged according to 1983 American Joint Committee on Cancer criteria) or gastroesophageal junction were treated with concomitant radiation and chemotherapy followed by esophagectomy. METHODS: Radiotherapy was administered in daily 2-gray (Gy) fractions 5 days a week until a total of 60 Gy was reached. 5-fluorouracil (5-FU) was infused continuously at a dose of 1000 mg/m2/day for 96 hours on Days 2-5 and 28-31. On Day 2, a 10 mg/m2 bolus of mitomycin was injected intravenously. Esophagectomy was performed 4-8 weeks following completion of the radiotherapy. RESULTS: During the 18-month study period (August 1991 through January 1993), 46 eligible patients were accrued from 21 institutions. Eight patients were Stage I and 38 Stage II. Eighty-seven percent of patients (40 of 46) received 6000 centigray (cGy), and all received >5000 cGy. Seventy-eight percent of patients (36 of 46) received >90% of the planned 5-FU dose. Follow-up ranged from 11 to 36 months (median, 22 months). There were eight treatment-related deaths; two were preoperative (from adult respiratory distress syndrome) and six were postoperative. Complete or partial response prior to esophagectomy was observed in 63% of cases, stable disease in 15%, and progression in 20%. Thirty-three patients underwent esophagectomy (transhiatal, n=14; Ivor Lewis, n=16; other, n=3). No tumor was found in the specimens resected from 8 of these 33 patients; this represented a pathologic complete response rate of 17% overall and 24% for those who underwent esophagectomy. Overall median survival was 16.6 months, 1-year survival 57%, and 2-year survival 27%. Survival was significantly worse for patients with circumferential cancers (median, 18.1 months vs. 8.3 months; P <0.05). CONCLUSION: High dose radiation therapy with concurrent 5-FU and mitomycin may be administered to patients with esophageal adenocarcinoma with acceptable morbidity. However, in a cooperative group setting, esophagogastrectomy following intensive chemoradiotherapy is associated with excessive morbidity and mortality. Circumferential tumor growth is a significant adverse prognostic factor.

Adenocarcinoma↗
PubMed2001

Benefit of surgery after chemoradiotherapy in stage IIIB (T4 and/or N3) non-small cell lung cancer.

OBJECTIVE: The purpose of this study was to evaluate postchemoradiotherapy surgery in stage IIIB non-small cell lung cancer. METHODS: Forty patients with stage IIIB non-small cell lung cancer were included in this phase II study. A preoperative diagnosis of stage IIIB cancer was based on mediastinoscopy or a thoracotomy in all patients. Induction treatment included two cycles of cisplatin (100 mg/m(2), day 1), 5-fluorouracil (1 g/m(2), days 1-3), and vinblastine (4 mg/m(2), day 1) combined with 42 Gy of hyperfractionated radiotherapy delivering 21 Gy in two sessions. Patients with a clinical response were offered surgery. RESULTS: The minimum follow-up for survivors was 48 months. Thirty patients had a T4 lesion and 18 had N3 disease. Twenty-nine patients (73%) had a clinical objective tumor response after induction treatment. These 29 patients underwent thoracotomy, and a complete resection was performed in 23 (58%). Two postoperative deaths occurred (7%). Four patients had a pathologic complete response at the time of surgery (10%). The 5-year survival is 19% for the overall population. When only patients who had persistent viable tumor cells at surgery are considered (n = 25), the 5-year survival is 28%. The 5-year survival is 42% for patients having no mediastinal lymph node involvement at the time of surgery and being treated with complete resection. CONCLUSION: This study shows that surgery, when feasible, is associated with a 28% long-term survival for patients in whom chemoradiotherapy alone fails to control disease.

Adult↗
PubMed2002

Predictive factors for response to neoadjuvant therapy in patients with oesophageal cancer.

BACKGROUND: Preoperative radio-chemotherapy (RCX) was introduced to improve the outcome of patients with oesophageal cancer (EC), but conflicting results have been released. Some 20-30% of patients show a complete pathological response, however, the perioperative morbidity and mortality is increased. To search for factors indicating response prior to the onset of RCX we investigated the proliferative activity (MIB-1), the expression of vascular endothelial growth factor (VEGF), and the capillary density (CD34) in samples of EC obtained by endoscopy prior to the start of the treatment. METHODS: Forty-six (MIB-1) and 21 (VEGF, CD34) tissue specimens of ECs were available from 56 patients undergoing pretherapeutic endoscopy, RCX and surgery. Perioperative morbidity was divided into surgery and non-surgery related morbidity. MIB-1, VEGF and CD34 expression were investigated immunohistochemically. Multivariate analysis was carried out to prove independence of investigated variables. RESULTS: Postoperative morbidity was noticed in 54 of 56 operated patients. Eight of 56 patients who received RCX died in hospital. Survival was significantly different between the group of complete responders (n=14) and non-responders (n=23; P=0.0026). None of the investigated tumour samples from patients with a complete response (CR) had a proliferation index of less than 45. Tumour samples from patients with a CR showed a VEGF expression of 10.7 compared with 36.58 of tumours with no response (P=0.035). CD34 expression showed a correlation with VEGF expression. The relation of mean indices of VEGF expression and proliferative activity in tumours from patients with complete, partial or no response was 10.7:58.8, 18.3:53.8 and 36.6:43.5, respectively. CONCLUSIONS: According to these results, it may be expected that tumours with a VEGF/MIB-1 ratio of 1:6 or less prior to RCX will respond to this therapy.

Adenocarcinoma↗
PubMed1999

Carboplatin, ifosfamide, and vinorelbine in the treatment of advanced non-small-cell lung cancer: a phase II study.

The authors evaluated the efficacy and toxicity of the combination of carboplatin, ifosfamide, and vinorelbine in the treatment of advanced non-small-cell lung cancer. From March 1994 through March 1996, 56 previously untreated patients with stage IIIB or stage IV non-small-cell lung cancer with measurable lesions and good performance status were entered in the study. The chemotherapy schedule was as follows: carboplatin 100 mg/m2 and ifosfamide 1,500 mg/m2 with mesna on days 1, 2, and 3; vinorelbine 25 mg/m2 on days 1 and 8, every 21 days; for a total of six courses. Among 55 evaluable patients there were three complete responses (5%) and 22 partial responses (40%), for a response rate of 45% (95% confidence interval, 32-59%). The median response duration was 10.3 months (range, 2.5-27.7 months), and median survival time was 11.3 months (range, 1.1-28.1 months). The survival rate at 1 year was 48%. Toxicity included hematologic toxicity in 60% of the 247 treatment cycles administered, nausea, alopecia, and neuropathy. One pathologic complete response was observed in a patient with stage IIIB disease who became operable after four courses of chemotherapy. The outpatient treatment with carboplatin, ifosfamide, and vinorelbine shows activity in advanced non-small-cell lung cancer. The toxicity was well tolerated by patients with a good performance status.

Adult↗
PubMed1998

High-dose chemotherapy and haematopoietic stem cell transplantation for inflammatory breast cancer: pathologic response and outcome.

Inflammatory breast cancer still has a poor prognosis despite improvements related to the introduction of neoadjuvant chemotherapy. The purpose of this study was to evaluate pathologic response rate and outcome of patients receiving high-dose chemotherapy with haematopoietic stem cell support for IBC. Seventeen consecutive patients with IBC received an association of mitoxantrone (36 mg/m2), cyclophosphamide (120 mg/kg), melphalan (140 mg/m2), with stem cell transplantation (SCT) following four to five cycles of cyclophosphamide (1000 mg/m2), doxorubicin (75 mg/m2) and 5FU (500 mg/m2). Mastectomy was performed a median of 2 months (range 1.5-45) after high-dose chemotherapy and was followed by radiotherapy. Macroscopic and microscopic pathologic complete response rates were respectively 56 and 39%. With a median follow-up of 36 months (range 17-52) 10 patients remain alive free of disease and seven patients have relapsed. Two relapses occurred in the group of patients with pathologic CR and five in the group with residual tumour. These results show that high-dose chemotherapy (HDC) with alkylating agents followed by SCT allows a very high tumour eradication in inflammatory breast cancer, suggesting a possible global benefit in progression-free survival and survival which remains to be demonstrated prospectively.

Adult↗
PubMed2005

Gene expression profiling of localized esophageal carcinomas: association with pathologic response to preoperative chemoradiation.

PURPOSE: Patients with localized esophageal carcinoma have a 5-year survival rate of less than 20%. Patients are often treated similarly (ie, with preoperative chemoradiotherapy) but the outcomes vary greatly. Chemoradiotherapy and surgery can result in significant undesirable consequences. Currently, however, there are no tools to help select optimum therapy. We hypothesized that gene expression profiling could provide clues and biomarkers for selection of therapy. METHODS: Pretreatment endoscopic cancer biopsies from 19 patients (16 with adenocarcinoma, two with squamous cell carcinoma, and one with adenosquamous carcinoma) enrolled onto a preoperative chemoradiotherapy protocol were profiled using oligonucleotide microarrays. Surgical specimens following therapy were assessed for the degree of pathologic response. On the basis of array data, selected genes were analyzed by polymerase chain reaction. RESULTS: Unsupervised hierarchical cluster analysis segregated the cancers into two molecular subtypes, each consisting 10 and nine specimens, respectively. Most cancers (five of six) that had pathologic complete response (pathCR) clustered in molecular subtype I. Subtype II, with one exception, consisted cancers that had less than pathCR (< pathCR). Using a combination marker approach, levels of PERP, S100A2, and SPRR3 allowed discrimination of pathCR from < pathCR with high sensitivity and specificity (85%). Pathway analysis identified apoptotic pathway as one of the key functions downregulated in molecular type II in comparison with type I. CONCLUSION: These encouraging, albeit preliminary, data suggest that expression profiling may distinguish cancers with different pathologic outcome. This is the first report to show subtypes of esophageal cancers with distinct molecular signatures. The potential of PERP, S100A2, and SPRR3 as biomarkers of pathCR warrants further validation.

Adenocarcinoma↗
PubMed2002

[Prospective phase II study of neoadjuvant radiochemotherapy in advanced operable carcinoma of the mouth cavity. 3-year outcome].

PURPOSE: The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrease the incidence of distant metastases. Regimens containing cisplatin/5-FU chemotherapy are widely accepted as standard treatment in advanced head and neck cancer. Most studies reported promising response and survival data, but also severe mucosal toxicity. In recent years the newly developed drug Taxol demonstrated interesting activity in head and neck cancer as a single agent as well as in combination drug regimens. In the present outpatient phase II trial, we investigated the combination of Taxol/carboplatin with 40 Gy radiotherapy in a neoadjuvant setting of operable stage III/IV squamous cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Fifty-three patients were enrolled in this trial during the period from May 1998 to October 2000 and received five cycles weekly of Taxol (40 mg/m2) and carboplatin (AUC 1.5) with conventional radiotherapy (40 Gy). Within 3-4 weeks after chemoradiotherapy resection of the primary tumor and the regional neck nodes was performed. RESULTS: Fifty-two patients were evaluable for toxicity and response. Complete response was observed in 31 of 52 patients (CR 60%), and partial remission was seen in 21 of 52 patients (PR 40%). In 30 of 52 patients complete pathologic response (pCR 58%) was documented in the resection specimens. The 1-, 2-, and 3-year overall survival rate was calculated as 84%. CONCLUSION: Our present results demonstrated impressive clinical and pathological response rates of concurrent Taxol/carboplatin and radiotherapy as a preoperative treatment modality in advanced oral and oropharyngeal cancer.

Adult↗
PubMed1995

Locally advanced non-metastatic breast cancer: analysis of prognostic factors in 125 patients homogeneously treated with a combined modality approach.

125 stage III breast cancer patients, including 51 cases of inflammatory carcinoma, were treated with the following combined modality approach: three courses of primary 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) chemotherapy followed by locoregional treatment and subsequent adjuvant chemotherapy consisting of three courses of FAC alternating with three courses of cyclophosphamide, methotrexate, 5-fluorouracil (CMF). Clinical response to primary FAC was 65% (complete 10%). Residual tumour mass in the mastectomy specimen was > 1 and < or = 1 cm in 82 and 18% of cases, respectively. Complete pathological response following primary chemotherapy was achieved in only 3.5% of cases. After primary FAC and local treatment, 97% of patients were disease-free. Overall survival (S) and progression-free survival (PFS) at 5 years were 56 and 34%, respectively. Univariate analysis showed that age, receptor status and clinical and pathological response to primary chemotherapy did not appear to influence treatment outcome significantly, whereas stage, presence of inflammatory disease and number of involved nodes had a significant impact on both S and PFS.

Adenocarcinoma↗
PubMed2003

Celecoxib, a selective cyclo-oxygenase-2 inhibitor, enhances the response to preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer.

PURPOSE: Preclinical studies suggest that treatment with a selective cyclo-oxygenase-2 (COX-2) inhibitor may augment the antitumor effects of chemotherapy. In this study, patients with non-small-cell lung cancer (NSCLC) were preoperatively treated with celecoxib in combination with chemotherapy. End points were toxicity, response rates, and measurement of intratumoral levels of prostaglandin E2 (PGE2). METHODS: In this phase II trial, 29 patients with stages IB to IIIA NSCLC were treated with two preoperative cycles of paclitaxel and carboplatin, as well as daily celecoxib, followed by surgical resection. Levels of PGE2 in the primary tumors and adjacent normal lung tissue were compared in 17 study patients versus 13 controls, who received preoperative paclitaxel/carboplatin without celecoxib. RESULTS: All patients completed preoperative chemotherapy, and 26 completed preoperative celecoxib. The overall clinical response rate was 65% (48% with partial response; 17% with complete response). Grade 3 or 4 neutropenia was observed in 18 patients (62%). Twenty-eight patients were explored and underwent complete resection of their tumors. There were no complete pathologic responses, but seven patients (24%) had minimal residual microscopic disease. The addition of celecoxib to a regimen of paclitaxel and carboplatin abrogated the marked increase in levels of PGE2 detected in primary tumors after treatment with paclitaxel and carboplatin alone. CONCLUSION: In comparison with historically reported response rates, these data suggest that the addition of a selective COX-2 inhibitor may enhance the response to preoperative paclitaxel and carboplatin in patients with NSCLC. Moreover, treatment with celecoxib 400 mg twice daily was sufficient to normalize the increase in PGE2 levels found in NSCLC patients after treatment with paclitaxel and carboplatin. Confirmatory trials are planned.

Adult↗
PubMed2006

Phase II study of neoadjuvant docetaxel/ vinorelbine followed by surgery and adjuvant doxorubicin/cyclophosphamide in women with stage II/III breast cancer.

BACKGROUND: The purpose of this study was to evaluate the combination of docetaxel plus vinorelbine as neoadjuvant chemotherapy for stage II/III locally advanced breast cancer. PATIENTS AND METHODS: Eligible women with stage IIA-IIIB or locoregional stage IV breast cancer were treated before surgery with 6 cycles of docetaxel 60 mg/m2 and vinorelbine 45 mg/m2, repeated every 2 weeks with granulocyte colony-stimulating factor and quinolone prophylaxis. Pathologic complete response (pCR), viewed as an early surrogate for disease-free and overall survival, was the primary efficacy endpoint. Sixty patients were enrolled; 60% had T3 or T4 lesions, 67% had clinically palpable lymph nodes, and 52% were hormone receptor positive. RESULTS: Fifty-nine patients were evaluable for pathologic response; 16 (27%) exhibited pCR in the breast alone (T0 Tis NX), 20% exhibited a pCR in the breast and lymph nodes (T0 Tis N0), 24 (41%) had < 5 mm of residual tumor, and 28 (47%) had node-negative disease at surgery. Relative dose intensity was 96% for docetaxel and 95% for vinorelbine. The clinical response rate was 98% (59 of 60 patients), including 38 complete responses (63%). Grade 3/4 neutropenia (95%), neutropenic fever (22%), mucositis (5%), and pulmonary toxicity (5%) occurred in >or= 5% of patients. Constipation was seen early but became insignificant after incorporating a prophylactic laxative regimen. Other toxicities have been minimal. CONCLUSION: With a clinical response rate of 98% and an in-breast pCR rate of 27%, docetaxel/vinorelbine is among the most active neoadjuvant regimens reported for locally advanced breast cancer. Docetaxel/vinorelbine can be administered in a dose-dense fashion while maintaining relative dose intensity. However, there was a significant incidence of fever and neutropenia despite the use of prophylactic growth factors and quinolones, indicating that lower doses of docetaxel/vinorelbine should be evaluated in future studies.

Adult↗
PubMed2006

Issues in the assessment of the pathologic effect of primary systemic therapy for breast cancer.

BACKGROUND: Emerging evidence suggests that induction of pathologic complete response (pCR) after primary systemic therapy (PST) is, at least to some extent, predictive of survival. However, standards for processing surgical specimens and for histopathologic evaluation of the pathologic response to therapy appear to be lacking. METHODS: To perform a systematic review of representative articles on this topic, a computerized (MEDLINE) search was undertaken followed by a manual search based on the reference lists of the publications identified. RESULTS: Several classification systems have been used to assess pathologic response to PST, the term pCR has not been applied in a consistent standardized manner, and only limited information is available about the reliability and validity of these classification systems. However, definitions of pCR can be summarized as follows: near pCR, only focal invasive tumor residues in the removed breast; quasi pCR, total or near total disappearance of invasive tumor in the removed breast; pCRinv, only in situ tumor residual in the removed breast; comprehensive pCR, no evidence of residual invasive tumor in the removed breast; strict pCR, disappearance of all tumor cells in the removed breast; comprehensive pCR (br+n), no evidence of residual invasive tumor in the breast and axillary nodes; strict pCR (br+n), no malignant tumor cells in the removed breast and axillary nodes. Comparison of the use of the term "pCR" in various trials reveals that it is not applied equivalently in these studies. CONCLUSION: Assessment of pCR needs to be standardized, with verification for reliability and validity. For now, the non-equivalency in the definition of pCR should be taken into account when comparing the results of PST.

Antineoplastic Agents↗
PubMed2006

Predicting response to primary chemotherapy: gene expression profiling of paraffin-embedded core biopsy tissue.

PURPOSE: Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment. We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy. PATIENTS AND METHODS: Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks x 3 and docetaxel 40 mg/M2 weekly x 6; treatment order was randomly assigned. Pretreatment core biopsy samples were interrogated for genes that might correlate with pathologic complete response (pCR). In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined. RESULTS: Of 70 patients enrolled in the parent trial, core biopsies samples with sufficient RNA for gene analyses were available from 45 patients; 9 (20%) had inflammatory breast cancer (IBC). Six (14%) patients achieved a pCR. Twenty-two of the 274 candidate genes assessed correlated with pCR (p < 0.05). Genes correlating with pCR could be grouped into three large clusters: angiogenesis-related genes, proliferation related genes, and invasion-related genes. Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR. In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer; twenty-four (9%) of the genes were differentially expressed (p < 0.05), 5 were upregulated and 19 were downregulated in IBC. CONCLUSION: Gene expression analysis on core biopsy samples is feasible and identifies candidate genes that correlate with pCR to primary chemotherapy. Gene expression in IBC differs significantly from noninflammatory breast cancer.

Adult↗
PubMed2007

Kinetics of serum HER-2/neu changes in patients with HER-2-positive primary breast cancer after initiation of primary chemotherapy.

BACKGROUND: The purpose of the study was to determine the utility of quantitation of the extracellular domain (ECD) of the HER-2/neu receptor in the serum for predicting response to treatment in patients with primary breast cancer receiving neoadjuvant therapy. METHODS: HER-2/neu ECD was measured in sera obtained from 39 patients with HER-2-amplified stage II-III primary breast cancer undergoing neoadjuvant chemotherapy. Patients were randomly assigned to either 4 cycles of paclitaxel followed by 4 cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) (n = 10) or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks (n = 29). Changes in HER-2 ECD were monitored with the Bayer HER-2/neu assay over 6 months and correlated with pathological response to treatment. RESULTS: Before initiation of chemotherapy, 28.2% of patients had elevated concentration of the HER-2 ECD (>15 ng/mL). The median baseline serum HER-2 ECD concentration was 13.6 ng/mL (mean +/- SD, 20.3 +/- 35.5 ng/mL). A decrease in the median HER-2 ECD levels from baseline to Week 3 and from baseline to Week 6 of chemotherapy was seen regardless of treatment regimen. No significant difference in baseline HER-2 ECD levels was observed between the groups who achieved pathological complete response (pCR) and the group with residual disease (P = .41). However, a 9% drop from Week 3 to Week 6 after initial chemotherapy was predictive of pCR (P = .04). CONCLUSION: A decrease in serum HER-2 ECD levels early during treatment was associated with pathological response in patients receiving primary chemotherapy, particularly trastuzumab-based regimens. Serum HER-2 ECD levels may serve to monitor neoadjuvant therapy in HER-2-positive primary breast cancer.

Adult↗