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PubMed2005

[Feasibility of breast conservation surgery after neoadjuvant chemotherapy for breast cancer].

OBJECTIVE: To investigate the efficacy of neoadjuvant chemotherapy (NCT) and the feasibility of conservative breast surgery after reducing the size of a primary tumor by NCT in patients with operable breast cancer. METHODS: Thirty patients with stage IIB and IIIA breast cancer underwent NCT including epirubicin 60 mg/m(2) by intravenous injection on day 1 and paclitaxel 150 mg/m(2) by 3-hour continuous infusion on day 2 with 21 days as a cycle from July 2001 to April 2003. All patients received 3 - 4 cycles of NCT. Breast conservation treatment or modified mastectomy was performed after the tumor was reduced to less than 3 cm in diameter. The nonresponders received modified mastectomy. RESULTS: The overall response rate (ORR) was 93% (28/30) for the primary tumors of breast, Fifteen patients (50%) obtained clinical complete response (cCR), including 7 cases (23%) with pathologic complete response (pCR). Thirteen cases (43%) achieved clinical partial response (cPR), and 2 (7%) no change (NC). No case showed progression of disease. Twenty-six (87%) cases were downstaged according to the TNM system classification. The median initial tumor size was 4 cm (3 - 10 cm) before NCT and was reduced to 0.8 cm (0 - 6 cm) after NCT. All 30 patients received operation. Eighteen (60%) of them were candidates for breast conserving therapy, and actually only 11 (37%) selected such surgery. CONCLUSION: An effective treatment for operable breast cancer, NCT with epirubicin plus paclitaxel results in significant downstaging or eliminating of primary tumors in breast cancer, thus expanding the indication of breast conservation therapy.

Adult↗
PubMed2003

Preoperative therapy with trastuzumab and paclitaxel followed by sequential adjuvant doxorubicin/cyclophosphamide for HER2 overexpressing stage II or III breast cancer: a pilot study.

PURPOSE: Trastuzumab combined with chemotherapy improves outcomes for women with human epidermal growth factor receptor 2 (HER2) overexpressing advanced breast cancer. We conducted a pilot study of preoperative trastuzumab and paclitaxel, followed by surgery and adjuvant doxorubicin and cyclophosphamide chemotherapy in earlier stage breast cancer. PATIENTS AND METHODS: Patients with HER2-positive (2+ or 3+ by immunohistochemistry) stage II or III breast cancer received preoperative trastuzumab (4 mg/kg x 1, then 2 mg/kg/wk x 11) in combination with paclitaxel (175 mg/m(2) every 3 weeks x 4). Patients received adjuvant doxorubicin and cyclophosphamide chemotherapy following definitive breast surgery. Clinical and pathologic response rates were determined after preoperative therapy. Left ventricular ejection fraction and circulating levels of HER2 extracellular domain were measured serially. RESULTS: Preoperative trastuzumab and paclitaxel achieved clinical response in 75% and complete pathologic response in 18% of the 40 women on study. HER2 3+ tumors were more likely to respond than 2+ tumors (84% v 38%). No unexpected treatment-related noncardiac toxicity was encountered. Four patients developed grade 2 cardiotoxicity (asymptomatic declines in left ventricular ejection fraction). Baseline HER2 extracellular domain was elevated in 24% of patients and declined with preoperative therapy. Immunohistochemical analyses of posttherapy tumor specimens indicated varying patterns of HER2 expression following trastuzumab-based treatment. CONCLUSION: Preoperative trastuzumab and paclitaxel is active against HER2 overexpressing early-stage breast cancer and may be feasible as part of a sequential treatment program including anthracyclines. The observed changes in cardiac function merit further investigation. Correlative analyses of HER2 status may facilitate understanding of tumor response and resistance to targeted therapy.

Adult↗
PubMed1995

Phase II study of intraperitoneal cisplatin plus systemic etoposide as second-line treatment in patients with small volume residual ovarian cancer.

The efficacy and toxicity of intraperitoneal (i.p.) cisplatin plus systemic etoposide were studied in 36 patients with small (< 2 cm) residual i.p. ovarian cancer after achieving a partial response to platinum-based, first-line chemotherapy. Treatment comprised 90 mg/m2 i.p. cisplatin with intravenous (i.v.) sodium thiosulphate (day 1) and 600-800 mg/m2 i.v. etoposide (days 1 and 2), every 4 weeks for four to six cycles. 7 patients achieved a pathological complete response (pCR), one a pathological partial response and 16 were clinically stable without evidence of disease. After a median follow-up of 13 months, the median progression-free survival (PFS) was 11 months (95% confidence interval 7-16 months). The actuarial PFS at 24 months is 22% (95% confidence interval 8-36%). Three of six relapses after achieving a pCR (50%) were sited i.p., and 9 of 14 other patients with disease progression (64%) had an i.p. relapse, indicating insufficient local efficacy. There was no renal toxicity, but grade 3-4 leucopenia occurred in 63% and grade 3-4 thrombocytopenia in 8% of cycles, while nausea, vomiting and complete alopecia were common. Although side-effects were acceptable, the efficacy of treatment with i.p. cisplatin plus i.v. etoposide is limited.

Administration, Topical↗
PubMed2004

p53 expression as a prognostic marker in inflammatory breast cancer.

PURPOSE: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer. Nuclear expression of p53 protein in breast cancer correlates with more aggressive tumors. We retrospectively analyze the expression of p53 as a prognostic marker to predict pathological complete response and survival in patients with IBC. EXPERIMENTAL DESIGN: Fifty-nine patients with IBC were treated from January 1994 to April 2000. Forty-eight patients were included. Diagnostic core biopsies were taken before treatment was started. Expression of hormone receptors and p53 was determined by immunohistochemistry. All patients received an anthracycline-based regimen preoperatively; 22 patients (46%) also received paclitaxel. Forty-four patients (92%) achieved an objective clinical response and underwent mastectomies. RESULTS: Median age at diagnosis was 48 years. Thirty patients (63%) had hormone receptor-negative tumors. Twenty-eight patients (58%) had p53-positive tumors, and 20 patients (42%) had p53-negative tumors. Nine patients (19%) achieved a pathological complete response. At a median follow-up of 77 months, 28 recurrences (58%) and 26 deaths (54%) had occurred. Patients with p53-positive tumors were younger (P=0.02) and tended to have lower 5-year progression-free survival rates (35% versus 55%; P=0.3) and overall survival rates (44% versus 54%; P=0.4). CONCLUSIONS: This retrospective analysis demonstrates that nuclear p53 protein expression may represent an adverse prognostic marker in IBC and may provide a valuable tool for selecting treatment for this aggressive disease.

Adult↗
PubMed2006

Complementary use of local excision and transanal endoscopic microsurgery for rectal cancer after neoadjuvant chemoradiation.

BACKGROUND: Neoadjuvant therapies have significantly improved local control and survival of patients with rectal cancer. Nevertheless, although a complete pathologic response can be achieved in 30% of cases, a transabdominal surgical resection is always required. This study aimed, for the first time, to test in the literature the feasibility of local excision combined with transanal endoscopic microsurgery (TEM) as a surgical option for patients treated with neoadjuvant chemoradiation. METHODS: Between July 1997 and December 2002, 30 patients with rectal cancer affected by an extraperitoneal tumor entered a protocol consisting of neoadjuvant chemoradiation followed by surgery. The surgical treatment, consisting of open surgery, local excision, or TEM, was planned according to the patient's clinical response after chemoradiation and distance from the anal verge. RESULTS: A significant clinical downstaging was observed in eight patients. Five of these patients underwent TEM, and three had local excision. Consequently, open surgery was performed for 22 patients. Histology showed six cases of complete pathologic response: three in the open surgery group and three in the transanal excision group. After a mean follow-up period of 47 months, the disease-free survival rate was 77% in the open surgery group and 100% in TEM or local excision group. CONCLUSIONS: The findings suggest the complementary feasibility of TEM and local excision after neoadjuvant chemoradiation. However, randomized trials are needed to confirm the oncologic safety of this approach.

Aged↗
PubMed2002

Dose-response relationship between probability of pathologic tumor control and glucose metabolic rate measured with FDG PET after preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer.

PURPOSE: To determine the dose-response relationship between the probability of tumor control on the basis of pathologic tumor response (pTCP) and the residual metabolic rate of glucose (MRglc) in response to preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer and to define the level of residual MRglc that corresponds to pTCP 50% and pTCP > or = 95%. METHODS AND MATERIALS: Quantitative dynamic 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography was performed to measure regional MRglc at the primary lesion before and 2 weeks after preoperative chemoradiotherapy in an initial group of 13 patients with locally advanced NSCLC. A simplified kinetic method was developed subsequently from the initial dynamic study and used in the subsequent 16 patients. The preoperative radiotherapy programs consisted of (1) a split course of 42 Gy in 28 fractions within a period of 28 days using a twice-daily treatment schedule for Stage IIIA(N2) NSCLC (n = 18) and (2) standard once-daily radiation schedule of 45-63 Gy in 25-35 fractions during a 5-7-week period (n = 11). The preoperative chemotherapy regimens included two cycles of cisplatin, vinblastine, and 5-fluorouracil (n = 24), cisplatin and etoposide (n = 2), and cisplatin, Taxol, and 5-fluorouracil (n = 3). Patients free of tumor progression after preoperative chemoradiotherapy underwent surgery. The degree of residual MRglc measured 2 weeks after preoperative chemoradiotherapy and 2 weeks before surgery was correlated with the pathologic tumor response. The relationship between MRglc and pTCP was modeled using logistic regression. RESULTS: Of 32 patients entered into the study, 29 (16 men and 13 women; 30 lesions) were evaluated for the correlation between residual MRglc and pathologic tumor response. Three patients did not participate in the second study because of a steady decline in general condition. The median age was 60 years (range 42-78). One of the 29 patients had two separate lesions, and MRglc was measured in each separately. The tumor histologic types included squamous cell carcinoma (n = 9), adenocarcinoma (n = 13), large cell carcinoma (n = 6), and poorly differentiated carcinoma (n = 2). The extent of the primary and nodal disease was as follows: Stage IIB (T3N0M0), Pancoast tumor (n = 2); Stage IIIA, T2-T3N2M0 (n = 18); Stage IIIB: T1-T3N3M0 (n = 5) and T4N0M0 (n = 2); a second lesion, T1 (n = 1); and localized stump recurrence (n = 2). A pathologically complete response was obtained in 14 (47%) of the 30 lesions. The remaining 16 lesions had residual cancer. The mean baseline value of the maximal MRglc was 0.333 +/- 0.087 micromol/min/g (n = 16), and it was reduced to 0.0957 +/- 0.059 micromol/min/g 2 weeks after chemoradiotherapy (p = 0.011). The correlation between residual MRglc and pTCP was made using an increment value of 0.02 micromol/min/g between the maximal and minimal values of MRglc. A pathologically complete response was obtained in 6 of 6 patients with residual MRglc of < or = 0.050 micromol/min/g, 3 of 4 with < or = 0.070, 4 of 7 with < or = 0.090, 0 of 4 with < or = 0.110, 1 of 3 with < or = 0.130, and 0 of 6 with > or = 0.130 micromol/min/g. The fitted logistic model showed that residual MRglc corresponding to pTCP 50% and pTCP > or = 95% was 0.076 and < or = 0.040 micromol/min/g, respectively. CONCLUSION: The correlation between the gradient of residual MRglc after chemoradiotherapy and pTCP is an inverse dose-response relationship. Residual MRglc of 0.076 and < or = 0.040 micromol/min/g, representing pTCP 50% and pTCP > or = 95%, respectively, may be useful surrogate markers for the tumor response to radiotherapy or chemoradiotherapy in lung cancer.

Adult↗
PubMed1997

Angiographic response of locally advanced soft-tissue sarcoma following hyperthermic isolated limb perfusion with tumor necrosis factor.

BACKGROUND: Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and melphalan is associated with a dramatic anti-tumor effect in which the neo-vascularization of the tumor is supposed to be the major target. The aim of the present study was to correlate the angiographic findings with the pathological response in patients undergoing HILP for locally advanced soft-tissue sarcoma. PATIENTS AND METHODS: Twenty-five patients, 14 male and 11 female, mean age 47 years (range 18-80) were studied. Angiographies were performed before and a median period of 7 weeks (range 4-14 weeks) after HILP. Eight weeks after perfusion, the residual tumor mass was resected and pathologically examined. The changes in tumor vascularization after treatment were scored and compared with the pathological response. RESULTS: All baseline angiograms showed a hypervascular tumor. After HILP, a normal angiography result (NA) was observed in 18 patients (72%) and an abnormal angiography result (AA) was observed in seven patients (28%). All patients with an NA showed a pathologically complete response (pCR) or a pathological partial response with > 90% necrosis of the tumor. Of seven patients with an AA, pathological examination showed a pCR in one patient, 10-50% viable tumor volume in four patients, and no pathological response after perfusion in two patients. A good correlation was seen between angiographic and pathological classification (p < 0.001). CONCLUSION: An angiography performed after hyperthermic isolated limb perfusion with TNF-alpha and melphalan provides a good indication, regardless of whether a good pathological response is expected.

Adolescent↗
PubMedDate not supplied

Role of Magnetic Resonance Imaging in the prediction of tumor response in patients with locally advanced breast cancer receiving neoadjuvant chemo-therapy.

PURPOSE: To evaluate if dynamic contrast enhanced magnetic resonance can predict the tumoural response in patients with breast cancer undergoing neoadjuvant chemotherapy. MATERIALS AND METHODS: Twenty-six patients with biopsy-proven locally advanced breast cancer underwent taxane-based neoadjuvant chemotherapy followed by radical surgery. MRI evaluations were carried out at baseline, after two of the four planned cycles of chemotherapy, and before surgical treatment. MR images, obtained with 1.5 T scanner and using dedicated surface multichannel coil (GEMS), were acquired by 3D SPGR sequences on the coronal plane before and after intravenous administration of gadolinium chelate by an automatic injector. The percent reduction of the early contrast uptake between the baseline and the second MRI was then calculated for every lesion and correlated with the outcome of interest (pCR). RESULTS: At baseline, we identified 26 lesions and two patterns of MRI enhancement: homogeneous (group 1, 14 patients) and peripheral ring-like (group 2, 12 patients). At surgery, pathological complete response was observed in 4 patients (2 patients group 1, 2 patients group 2). In group 1, the 2 cases of pCR showed a gs;70% reduction in the early contrast uptake between baseline examination and after two cycles of chemotherapy, whereas values <70% were seen in 12 cases of partial response (p=0.02). In group 2, the 2 cases of pCR showed a gs; 40% reduction in the early contrast uptake whereas all of the 10 cases of partial response had <40% reduction (p=0.02). CONCLUSIONS: In our series, the percent reduction in the early contrast uptake after two cycles of neoadjuvant chemotherapy was predictive of the achievement of a pathological complete response. However, we identified two distinct morphologic patterns associated with different cut-offs in the predictive value of the early contrast uptake reduction between baseline and intermediate examination.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Irinotecan/cisplatin followed by 5-FU/paclitaxel/radiotherapy and surgery in esophageal cancer.

Local-regional carcinoma of the esophagus is often diagnosed in advanced stages because the diagnosis is established when symptoms are severe. The prognosis of patients with local-regional carcinoma of the esophagus continues to be grim. While preoperative chemoradiotherapy increases the fraction of patients who achieve pathologic complete response, that percentage is approximately 25%. In an attempt to increase the number of patients with either no cancer in the surgical specimen or only microscopic cancer, we adopted a three-step strategy. The current study utilized up to two 6-week cycles of induction chemotherapy with irinotecan (CPT-11, Camptosar) and cisplatin as step 1. This was followed by concurrent radiotherapy and chemotherapy with continuous infusion fluorouracil (5-FU) and paclitaxel as step 2. Once the patients recovered from chemoradiotherapy, a preoperative evaluation was performed and surgery was attempted. All patients signed an informed consent prior to their participation on the study. A total of 43 patients were enrolled. The baseline endoscopic ultrasonography revealed that 36 patients had a T3 tumor, five patients had a T2 tumor, and two had a T1 tumor. Twenty-seven patients had node-positive cancer (N1). Thirty-nine (91%) of the 43 patients underwent surgery; all had an R0 (curative) resection. A pathologic complete response was noted in 12 of the 39 patients. In addition, 17 patients had only microscopic (< 10%) viable cancer in the specimen. Therefore, a significant pathologic response was seen in 29 (74%) of 39 taken to surgery or 29 (67%) of all 43 patients enrolled on the study. With a median follow up beyond 25 months, 20 patients remain alive and 12 patients remain free of cancer. Our preliminary data suggest that the proportion of patients with significant pathologic response can be increased by using the three-step strategy.

Adult↗
PubMed1997

Phase II trial of high-dose cisplatin plus ifosfamide as first-line followed by carboplatin as second-line treatment in epithelial ovarian carcinoma.

BACKGROUND: In a previous study of combined platinum and ifosfamide we found a pathologic complete response rate of 42%. The present study was to test whether the high response rate could be reproduced or even improved by combining high-dose cis-platinum and increased dose of ifosfamide. METHODS: Forty-two previously untreated ovarian cancer patients were included in the study. Cisplatin 50 mg/m2 and ifosfamide 2000 mg/m2 together with mesna 1200 mg/m2 were given daily, Day 1-3 every 4 weeks for six cycles, followed by second-look laparotomy. In the event of residual disease carboplatin was given every 4 weeks for a further six cycles. RESULTS: The pathologic complete response rate was 20% (8 of 41). Five of 26 patients achieved a further response on carboplatin. Hematologic and nonhematologic toxicity caused dose reduction in more than 90 and 50% of the patients, respectively. CONCLUSION: The results of this high-dose regimen equals those obtained with conventional, far less toxic, regimens. Only patients with potentially platinum-sensitive tumors achieved further response when crossed over to the analogue, which may indicate that prolonged treatment is better than increased dose. A randomized trial is still needed to assess the importance of dose intensity in ovarian cancer.

Adult↗
PubMed2005

Pre-operative chemoradiotherapy with oral tegafur-uracil and leucovorin for rectal cancer.

BACKGROUND: To evaluate the efficacy and toxicity of pre-operative radiotherapy (RT) combined with oral tegafur-uracil (UFUR) plus leucovorin (LV) in rectal cancer. PATIENTS: Sixty-five patients with rectal adenocarcinoma (clinical staged T2-4N0-2M0) received pelvic RT of 45 Gy in 20 fractions over 28 days. Concurrent chemotherapy consisted of UFUR (200 mg/m(2)/day) and LV (45 mg/day) on day 1-28. UFUR (250 mg/m(2)/day) and LV were continued on day 36-63. Surgery was performed on day 70. RESULTS: Sixty-three patients completed the concurrent chemoradiotherapy (CCRT) and 56 received curative or palliative surgery. Among the 52 patients receiving curative resection, downstaging (DS) occurred in 39 (75%), pathological complete response in 13 (25%), and sphincter preservation was achieved in 16 of 29 (55%) with lower-seated tumors. With a median follow-up time of 33 months, local failure developed in 4 (8%) and distant metastases occurred in 7 (14%). The 3-year overall survival was 92% and disease-free survival 76%. For all 65 patients, grade 3-4 diarrhea developed in 6 (9%) and grade 3-4 leucopenia observed in 2 (3%). CONCLUSIONS: Oral UFUR + LV administered with pre-operative RT are effective in tumor DS, pathological complete response, and sphincter preservation with tolerable toxicity in rectal cancer.

Adenocarcinoma↗
PubMed2004

Docetaxel and cisplatin as primary chemotherapy for treatment of locally advanced breast cancers.

A phase II trial was designed to evaluate the effectiveness of docetaxel/cisplatin as primary or neoadjuvant chemotherapy of locally advanced breast carcinoma (LABC). Patients with newly diagnosed breast cancers > or = 5 cm in size by palpation were treated with docetaxel/cisplatin, both at 70 mg/m2 intravenously every 21 days for 4 courses. Upon completion of chemotherapy, all patients underwent modified radical mastectomy with axillary nodal dissection. Pathologic complete response (pCR) was defined as absence of any invasive carcinoma in the breast. Standard AC (doxorubicin/cyclophosphamide) at 60 mg/m2 and 600 mg/m2, respectively, for 4 cycles was given as adjuvant therapy to maximally eradicate occult distant disease. Between March 1998 and October 2001, 57 women were entered onto this trial, 28 (49%) with inoperable T4 and inflammatory cancers. Pretreatment median tumor size was 9 cm. Thirty-six patients (63%) had estrogen receptor-positive tumors and 10 patients (18%) had tumors with HER2 overexpression. All tumors became operable after neoadjuvant chemotherapy. Pathologic complete response in the breast was achieved in 15 patients (26%) and pCR in the breast and the axilla was achieved in 11 patients (20%). All neoadjuvant chemotherapy courses were administered at full doses without treatment delays caused by toxicity. The most common side effects were hyperglycemia, anemia, and mild neuropathy. The results of this study suggest that the docetaxel/cisplatin combination can be an effective and well-tolerated induction treatment of LABC, even in very large mostly HER2-nonoverexpressing tumors.

Adult↗
PubMed2005

Neoadjuvant systemic therapy for breast cancer: an overview and review of recent clinical trials.

Neoadjuvant chemotherapy (NAC) is long established as part of the multi-modality management of locally advanced breast cancer or inflammatory breast cancer, leading to significantly improved outcome. Numerous recent studies have compared the use of anthracycline-based NAC with adjuvant chemotherapy in earlier-stage disease, and have shown equivalent disease-free and overall survival rates with increased breast conservation rates. These studies have also shown that a pathological complete response after NAC is associated with improved long-term outcome. More recently, the taxanes have been introduced into clinical trials of NAC with increased overall and pCR rates. However, there is no evidence that the addition of taxanes to neoadjuvant anthracycline-based chemotherapy significantly improves long-term disease free survival or overall survival. This paper reviews these trials, as well as trials of dose-dense and trastuzumab-containing NAC regimens. The review discusses the potential for NAC to replace prolonged adjuvant trials in the assessment of new therapeutic agents (using pathological complete response as a surrogate for long-term outcome), to be used as an in vivo chemosensitivity assay to guide further treatment, and to identify molecular markers that correlate with tumour sensitivity or resistance to chemotherapeutic agents so that the treatment of patients can be individualised.

Animals↗
PubMed1997

Preoperative radiotherapy (RT) for rectal cancer: predictive factors of tumor downstaging and residual tumor cell density (RTCD): prognostic implications.

PURPOSE: To determine predictive factors and prognostic value of tumor downstaging and tumor sterilization after preoperative RT for rectal cancer. METHODS AND MATERIALS: Between 1977 and 1994, 167 patients with a histologically proven adenocarcinoma (70 T2, 65 T3, 29 T4, and 3 local recurrences) underwent preoperative RT. Median dose was 44 Gy (5-73 Gy). Surgery was performed in a mean time of 5 weeks after RT. Pathologic specimens have been reviewed by the same pathologist in order to specify the modified Astler Coller classification (MAC), and to quantify the residual tumor cell density (RTCD). RESULTS: According to the MAC, there was 9 stage 0 (5%), 10 stage A (6%), 103 stage B1-B3 (62%), and 45 stage C1-C3 (27%) tumors. Seventeen percent and 56% of the patients who received a dose > or = 44 Gy had respectively a 0-A and a B tumor, compared to 4 and 69% in those who received a dose < 44 Gy (p = 0.04). Tumor differentiation and a longer interval before surgery were significantly associated with a more frequent downstaging, and preoperative staging correlated well to the postoperative pathological findings. According to the RTCD, 62 tumors (37%) showed no or only rare foci of residual tumor cells (Group 1); 62 (37%) showed an intermediate RTCD (Group 2); and 43 (26%) a high RTCD (Group 3). No predictive factor of RTCD was statistically significant. In univariate analysis, postoperative staging was a significant prognostic factor, with corresponding 5-year overall survival rates in 0-A, B, and C stages of 92, 67, and 26% (p < 0.01). RTCD was not a prognostic factor. However, overall and disease-free survival rates for patients with complete pathologic response of 83% at 2 and 5 years suggested a better outcome in this subgroup of patients. CONCLUSION: The favorable influence of higher doses of preoperative RT on pathologic stage has been observed. Tumor differentiation, preoperative classification and time before surgery were the other predictive factors of tumor downstaging. However, there was no predictive factor of complete pathologic response. Even after preoperative RT, postoperative staging remained a prognostic factor.

Adenocarcinoma↗
PubMed2003

Multimodality treatment for esophageal cancer: the role of surgery and neoadjuvant therapy.

Treatment of esophageal cancer has traditionally included surgery as the initial modality. Neoadjuvant chemoradiation therapy has been introduced with the goal of downstaging tumors before surgical resection; however, its role in esophageal cancer remains controversial. We report 116 patients who underwent esophagogastrectomy with reconstruction for carcinoma of the esophagus or esophagogastric junction over a 10-year period (January 1, 1990 to June 1, 2001). Forty patients underwent neoadjuvant radiation and chemotherapy followed by surgery. Hospital mortality in this group was 7.5 per cent, complete pathologic response (CPR) was 37.5 per cent, and overall 3- and 5-year survival rates were 47 and 38 per cent. Five-year survival in the 15 patients with CPR was 85 per cent. Five patients underwent neoadjuvant single-agent therapy (four chemotherapy and one radiation) followed by surgery, and none survived to 3 years. Seventy-one patients underwent surgery without neoadjuvant therapy. Hospital mortality in this group was 1.4 per cent, with 3- and 5-year survival of 21 and 17 per cent--a decreased long-term survival compared with the neoadjuvant therapy group despite the observation that patients who underwent neoadjuvant therapy had a larger tumor size on presentation (5.5 +/- 0.4 cm vs 3.8 +/- 0.2 cm; P = 0.002). Squamous cell carcinomas seemed to be more responsive to neoadjuvant radiation and chemotherapy followed by surgery than were adenocarcinomas, with a CPR of 44.4 versus 35.5 per cent; however, 5-year survival rates in these complete responders were not significantly different (100% and 78%, respectively; P = 0.97). We report that esophagogastrectomy in conjunction with neoadjuvant therapy results in increased survival compared with surgery without neoadjuvant therapy (P < 0.01), although there may be an increased perioperative mortality associated with neoadjuvant therapy. Further studies are needed to evaluate the role of preoperative chemoradiation and to better identify the pretreatment characteristics of patients with a complete pathological response.

Adenocarcinoma↗
PubMedDate not supplied

A new regimen of cisplatin, epirubicin and methotrexate (PEM-3) as primary chemotherapy for locally advanced bladder cancer.

In this phase II study, 41 patients with locally advanced urothelial bladder cancer (T2-4, N0, M0) were treated with primary chemotherapy (cisplatin, epirubicin, methotrexate: PEM-3). All the patients were assessable for response and toxicity. Clinical monitoring was performed with computerized tomography and cystoscopy. Nineteen clinical complete remissions (46%) and 10 partial remissions (24.5%) were obtained (CR + PR, 70.5%; 95% confidence interval, 57%-85%). Ten patients were considered to have clinically stable disease (24.5%), and 2 patients progressed (5%). Surgery after chemotherapy was performed in 22 cases: in 6 patients (27%) a pathologic complete response was achieved. The pathologic stage was lower than the initial clinical stage in 13 patients (59%). After a median follow-up of 3 years (range, 1-4), the median time to progression was 104 weeks. At this writing, 20 patients, 12 of which were submitted to surgery and 8 were not operated, are disease-free. The 3-year survival rate is 52%. No one had to interrupt the treatment because of toxicity. In conclusion, the PEM-3 regimen is a very active and well-tolerated regimen in locally advanced bladder cancer.

Aged↗
PubMed2002

[Tumor downstaging through preoperative chemoradiotherapy in locally advanced rectal cancer].

OBJECTIVE: To evaluate the impact of preoperative chemoradiotherapy on patients with locally advanced rectal cancer by clinical and pathological characteristics. METHODS: From July 1994 to May 1995, 36 patients with locally advanced rectal cancer were treated. Pathology: adenocarcinoma 27, mucinous adenocarcinoma 7 and ductal adenocarcinoma 6. The protocol was carried out in sequence of chemo-->radio-->surgery-->chemotherapy. The treatment began with preoperative chemotherapy with folinic acid 50 mg followed by 5-FU bolus of 300 mg/m2 given for two cycles on d1-5 and d22-26 before irradiation. Radiation therapy was delivered to a dose of 45 Gy, 1.8 Gy per fraction, 5 days a week. Surgery was done 4-6 weeks after this preoperative treatments. Another 2 to 4 cycles of chemotherapy were added 2 to 4 weeks after operation. Twenty-one patients were treated by Dixon's operation, 14 patients by Mile's operation and 1 by local tumorectomy through the rectum. Radical operation was performed in 29 patients and palliative resection was done in 7 patients. RESULTS: Grade III hematological toxicity was observed in only 2(5.6%) patients. No patient had grade III or IV acute toxicity in the gastrointestinal, skin or urological systems. All patients underwent surgery. The perioperative morbidity rate was 13.8% with no mortality or late toxicity. As a result of this preoperative management, the tumor was reduced by an average of 28.0%, with a complete pathological response in 4(11.1%) patients. In 28 CR + PR (77.8%) patients, a downstaging in 19(52.8%) patients was observed. Sixty percent of positive lymph nodes as assessed by transrectal ultrasonography before therapy became pathologically negative postoperatively, with the frequency of lymph node metastasis decreased by 46.0%(83.0% to 37.0%). CONCLUSION: Preoperative radiochemotherapy is proved as a safe method with a tolerable toxicity. Complete pathological response, shrinkage of the primary tumor and decrease in lymph node metastasis are observed after preoperative radiochemotherapeutic regimen. An overall benefit of downstaging the primary tumor and a greatly enhanced effect of surgery is enjoyed by the patients.

Adult↗
PubMed2003

Longer time interval between completion of neoadjuvant chemoradiation and surgical resection does not improve downstaging of rectal carcinoma.

PURPOSE: An interval of six to eight weeks between completion of preoperative chemoradiation therapy and surgical resection of advanced rectal cancer has been described. Our purpose was to determine whether a longer time interval between completion of therapy and resection increases tumor downstaging and affects perioperative morbidity. METHODS: Forty patients with advanced adenocarcinoma of the rectum underwent preoperative chemoradiation on a prospective trial with irinotecan (50 mg/m2), 5-fluorouracil (225 mg/m2), and concomitant external-beam radiation (45-54 Gy) followed by complete surgical resection of the tumor with total mesorectal excision. The time interval between completion of chemoradiation and surgical resection ranged from 28 to 97 days. The patients were divided into two groups with 33 eligible patients: Group A (4-week to 8-week time interval; 28-56 days) and Group B (10-week to 14-week interval; 67-97 days). Tumor downstaging was compared between these two groups. The number of patients downstaged by at least one T stage, those downstaged by at least one N stage, those with pathologic complete responses, and those with only residual microscopic tumor foci were compared. Postoperative length of stay, estimated blood loss, perioperative morbidity, and sphincter-sparing procedures were also compared. Chi-squared tests and Student's t-test were calculated. RESULTS: Group A had 19 patients, and Group B had 14 patients. Patient demographics were comparable. Mean age was 52 years, and 70 percent of patients were male. There were no deaths. There were no statistical differences in perioperative morbidity, with three anastomotic leaks in Group A. Tumors were downstaged in 58 percent of patients in Group A and 43 percent of those in Group B (P = 0.61). Nodal downstaging occurred in 78 percent of Group A and 67 percent of Group B (P = 0.9). The pathologic complete response rate was 21 percent in Group A and 14 percent in Group B (P = 0.97), and a residual microfocus of tumor was found in 33 percent of patients in Group A and 42 percent of those in Group B (P = 0.90). These differences were not statistically significant. CONCLUSIONS: Perioperative morbidity is not affected by longer intervals. A longer interval between completion of neoadjuvant chemoradiation and surgical resection may not increase the tumor response rate of advanced rectal cancer in this cohort.

Adenocarcinoma↗