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PubMedDate not supplied

Multimodal treatment for squamous cell esophageal cancer.

Preoperative chemotherapy (CTx) and combination radiochemotherapy (RTx/CTx) in patients with squamous cell esophageal carcinoma has recently received increasing attention. Although several prospective randomized trials could not show any benefit of neoadjuvant therapy in patients with potentially resectable tumors, preoperative CTx and combination RTx/CTx appear to increase the resection rate, the rate of complete tumor resection, and survival time in patients with locally advanced tumors. Most available studies show that a survival benefit from multimodal therapy can be expected primarily in patients who have a complete histopathologic response to preoperative treatment (i.e., no viable tumor in the resected specimen). Preoperative RTx/CTx increases the response rate and improves local tumor control compared to preoperative CTx alone, but it is associated with substantial perioperative mortality and morbidity. Distant tumor recurrences are insufficiently controlled with current combined modality protocols. These data indicate that neoadjuvant therapy must be considered investigational in patients with potentially resectable esophageal carcinoma but may soon become standard in patients with locally advanced tumors. Research must focus on modalities that allow pretherapeutic identification of those patients who will respond to neoadjuvant therapy. Furthermore, more effective and less toxic preoperative therapy regimens are required to increase the response rates and combat systemic recurrences. Finally, randomized prospective studies are essential to assess the role, extent, and timing of surgical resection for the combined modality approach to patients with squamous cell esophageal carcinoma.

Antineoplastic Agents↗

PubMedDate not supplied

[Is maximal androgenic blockade necessary in the treatment of prostatic cancer?].

As the literature data give arguments both pro and contra wide use of maximal androgenic block (MAB) in the treatment of prostatic cancer, the authors studied MAB in 200 patients. They came to the conclusion that MAB can be applied in patients with symptoms of disseminated prostatic cancer as neoadjuvant therapy before prostatectomy and as neoadjuvant and adjuvant therapy in planning radiotherapy.

Androgen Antagonists↗

PubMed2005

High risk of brain metastases in surgically staged IIIA non-small-cell lung cancer patients treated with surgery, chemotherapy, and radiation.

PURPOSE: Lung cancer is the leading cause of cancer mortality in the United States. We sought to review our experience with surgically staged IIIA (N2) non-small-cell lung cancer (NSCLC), focusing on the patterns of failure in consecutively treated patients from 1988 to 2000. PATIENTS AND METHODS: The records of 177 patients were reviewed. Collected data included stage, histology, use of chemotherapy and radiation, initial and subsequent sites of failure, and survival. One hundred twenty-four patients have died; follow-up time is 35 months among the remaining patients. RESULTS: The median survival from the time of surgery was 21.0 months, with a 3-year overall survival (OS) of 34%. Nodal downstaging to N0 disease correlated with OS and progression-free survival (PFS; P < .001). The most common site of recurrence was the brain. Thirty-four percent of patients recurred in the brain as their first site of failure, and 40% of patients developed brain metastases at some point in their course. In patients with nonsquamous histology and residual nodal involvement after neoadjuvant therapy, the risk of brain metastases was 53% at 3 years. CONCLUSION: Patients treated with neoadjuvant therapy for N2-positive stage IIIA NSCLC enjoy an advantage in both OS and PFS if their lymph node status is downstaged to N(0). Because brain metastases constitute the most common site of failure in these patients, future studies focusing on prophylaxis of brain metastases may improve the outcome in patients with stage IIIA NSCLC.

Adult↗

PubMed2002

Increased endocrine cells in treated rectal adenocarcinomas: a possible reflection of endocrine differentiation in tumor cells induced by chemotherapy and radiotherapy.

The presence of focal endocrine cells in colorectal adenocarcinoma is a relatively common phenomenon. However, endocrine differentiation in treated adenocarcinomas of the gastrointestinal tract has received little attention. We noted striking numbers of cells with endocrine morphology and phenotype in the residual tumor of six randomly encountered cases of rectal adenocarcinoma that were subjected to neoadjuvant therapy. All six cases had a substantial treatment response (> or =50%). To validate our initial observation and to explore its clinicopathologic significance, further morphologic and immunohistochemical studies were performed on 53 cases of rectal adenocarcinomas treated with preoperative radiation with (33 cases) or without (20 cases) chemotherapy. Pretreatment biopsies from 20 of the 53 cases and 79 resection specimens of rectal adenocarcinoma that received no neoadjuvant therapy were used as controls. Chromogranin positivity was identified in the posttreatment resection specimens in 36 of the 53 study cases (67.9%). Twenty of the 36 showed positive staining in > or =20% of the residual tumor cells. The chromogranin-positive cells in these cases often formed cords or nests. On hematoxylin and eosin sections these cells had markedly eosinophilic cytoplasm and round and uniform or sometimes pleomorphic nuclei with an often dense chromatin pattern. The proportion of chromogranin-positive cells was significantly associated with the extent of treatment response (p = 0.0005). Tumors treated with both chemotherapy and radiotherapy were more likely to have abundant chromogranin-positive cells compared with tumors treated with radiotherapy alone (p = 0.0004). In contrast, only 30% of the pretreatment biopsies and 17.7% of the control resection specimens of untreated rectal carcinomas showed chromogranin-positive cells, predominantly arranged as scattered individual positive cells, constituting <10% of the tumor. No significant correlation was observed between pretreatment and posttreatment specimens with regard to chromogranin positivity (p = 1.0). Ten of 15 patients (66.7%) whose resection specimens showed positive chromogranin staining failed to demonstrate any chromogranin positivity in their pretreatment biopsy specimens. In addition, groups or nests of chromogranin-positive cells noted in posttreatment specimens showed a very low Ki67 labeling index (<5%) but showed a frequency of abnormal p53 protein expression comparable with that observed in tumor foci resembling conventional adenocarcinoma (66.7% vs 62.5%). Our findings demonstrate that there is an increased frequency and density of cells with an endocrine phenotype in rectal adenocarcinomas that were subjected to neoadjuvant therapy and that the extent of endocrine cells appears proportional to the degree of treatment response. The possible mechanism for the increased endocrine cells in treated rectal adenocarcinomas may be related to induction of endocrine differentiation in tumor cells by cytotoxic insult.

Adenocarcinoma↗

PubMed1999

Micrometastases in esophagogastric cancer: high detection rate in resected rib segments.

BACKGROUND & AIMS: Micrometastases within bone marrow indicate a poor prognosis. We prospectively examined micrometastases in patients undergoing resection of esophagogastric cancers for (1) prevalence in rib marrow; (2) comparative detection rates in rib and iliac crest marrow; (3) responsiveness to neoadjuvant therapy; and (4) viability and tumorigenicity. METHODS: In 50 consecutive patients, marrow was obtained before manipulation of the primary tumor. Micrometastatic cells were detected by staining contaminant cytokeratin-18-positive cells. Viability and tumorigenicity were determined by culture and xenograft. RESULTS: Micrometastases were detected in rib marrow from 88% of patients (44 of 50). When bilateral iliac crest marrow was also obtained, micrometastases were found in 15% (4 of 27) compared with 89% (24 of 27) for ribs (P < 0.001). Detection rates were independent of histological type or nodal status and were similar in patients with and without neoadjuvant therapy. Metastatic cells were cultured from rib marrow of 5 of 7 patients and were tumorigenic in nude mice. CONCLUSIONS: Most patients undergoing resection of esophagogastric malignancies have micrometastases in rib marrow. Detection rates based on iliac crest marrow are underestimates. Hematogenous spread of metastatic cells is independent of histological type or nodal status. The metastatic cells are viable, tumorigenic, and resistant to neoadjuvant therapy.

Adenocarcinoma↗

PubMed1996

The role of neoadjuvant androgen deprivation prior to radical prostatectomy.

Androgen ablation prior to radical prostatectomy currently is under investigation with the goal of improving cancer control in patients with clinically treated localized prostate cancer. Results of several randomized studies have shown a significant pathologic downstaging and a decrease in the rate of positive surgical margins using neoadjuvant therapy in stage B cancers. Despite theoretic advantages, neoadjuvant therapy may have side effects and is associated with costs. Until long-term results of biologic and clinical failure rates are available, this approach should be considered investigational.

Androgen Antagonists↗

PubMed2006

[A case of advanced rectal cancer responding to l-Leucovorin (LV)/5-fluorouracil( 5-FU) therapy as neoadjuvant chemotherapy].

We report a case in which l-Leucovorin/5-fluorouracil (l-LV/5-FU) therapy was remarkably effective for advanced rectal cancer as neoadjuvant chemotherapy (NAC). A 54-year-old man complained of bloody stool and constipation,and was diagnosed as having stage IIIB advanced rectal cancer with N2 lymphnode metastases on July 31, 2003. Two cycles of NAC by l-LV/5-FU therapy were performed. On abdominal computed tomography (micro CT), the primary lesion in the rectum decreased 82% and the metastatic lymphnodes had disappeared. As we established a diagnosis of the downstaging for stage II, a lower anterior resection with D3 lymphnode dissection was performed on December 5, 2003. The pathological examination demonstrated II, mod, 1.8 x 2.2 cm, a1, ly1,v0, ow(-), aw(-), n0, stage II. We could allow curability-A resection. The pathological effect of chemotherapy was grade 2 in which cancer cells became necrotic, suggesting apoptosis. The postoperative course was good. Postoperatively, 3 cycles of l-LV/5-FU therapy were performed. Although the patient had to be followed with internal use of 5-FU 200 mg/day as an outpatient from June 2, 2004, to date, there has been no sign of recurrence during the 12-month follow-up after the operation. Moreover, no adverse by chemotherapy was seen during the treatment. Thus, NAC by this therapy may be useful for patients with advanced rectal cancer.

Adenocarcinoma↗

PubMed2000

Endoscopic ultrasound does not accurately assess pathologic stage of esophageal cancer after neoadjuvant chemoradiotherapy.

The accuracy of endoscopic ultrasound (EUS) for initial staging of esophageal cancer is widely accepted. There is, however, considerable variability in the reported accuracy of EUS for restaging of esophageal neoplasms after neoadjuvant therapy. From June 1995 through December 1999, we prospectively studied a series of 26 patients who underwent neoadjuvant treatment for esophageal cancer and were subsequently restaged by EUS before resection. Twenty-four patients had adenocarcinoma (92%), and two patients had squamous cell carcinoma (8%). EUS correctly predicted tumor stage in seven of 26 patients for an overall accuracy of 27 per cent. EUS overestimated the depth of tumor penetration in 18 patients (69%) and underestimated depth of penetration in one patient (4%). Lymph nodes were correctly staged in 15 of 26 patients for an overall accuracy of 58 per cent. Levels of sensitivity for detecting N0 and N1 disease were 44 per cent and 80 per cent respectively. Patients with a complete pathologic response were staged as T4N1 (one patient), T3N1 (three patients), T3N0 (one patient), and T2N1 (two patients). EUS cannot distinguish tumor involvement of the esophageal wall and lymph nodes from the postinflammatory changes that characterize effective neoadjuvant treatment. EUS is of limited utility in guiding clinical decision making after neoadjuvant therapy.

Adenocarcinoma↗

PubMed1998

Selection of local therapy after neoadjuvant chemotherapy in patients with stage IIIA,B breast cancer.

BACKGROUND: Stage IIIA,B breast cancer is commonly treated with neoadjuvant chemotherapy because of high objective response rates and improved operability. Criteria for subsequent selection of local therapy--mastectomy, radiotherapy, or both--are not well defined. We adopted a policy of selective local therapy based on rebiopsy of the breast and clinical axillary lymph node status at the time of best response to chemotherapy. METHODS: Between 1980 and 1993, 126 patients with stage IIIA,B breast cancer were treated with neoadjuvant chemotherapy and definitive local therapy. The long-term incidence of locoregional failure (in-breast, chest wall, axilla, supraclavicular, neck), relapse-free survival, and overall survival was determined. RESULTS: The overall clinical objective response rate to chemotherapy was 95.2%. Eighty-three patients underwent mastectomy, with negative margins achieved in 91.6%. Forty-two patients had breast preservation; the overall in-breast recurrence rate was 19.0% (8 of 42 patients). The overall locoregional recurrence rate by site was: chest wall-8.7% (11 of 126 patients), axilla-8.7% (11 of 126 patients), supraclavicular-5.6% (7 of 126 patients), and neck-4.0% (5 of 126 patients). The axillary recurrence rate was 6.6% (5 of 76 patients) for clinically negative axilla treated with radiotherapy only, and 12.0% (6 of 50 patients) for clinically positive axilla treated with surgery only. The overall long-term survival probabilities (6 years) according to stage were: stage IIIA-58.0%, stage IIIB(noninflam)-58.0%, stage IIIB(inflam)-36.0%. CONCLUSIONS: These findings support a selective approach to local therapy in patients with stage IIIA,B breast cancer. This approach provides local control in most patients, and allows for breast preservation and elimination of axillary dissection in selected patients.

Adult↗

PubMed2001

The role of 99mTc-MIBI scintigraphy in the assessment of MDR1 overexpression in patients with musculoskeletal sarcomas: comparison with therapy response.

The occurrence of multidrug resistance (MDR), which is in part due to the overexpression of P-glycoprotein (Pgp), is a major problem in neoadjuvant therapy of malignant musculoskeletal tumours. The aim of this study was to investigate the role of technetium-99m hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy for functional imaging of the MDR1 phenotype in patients with musculoskeletal sarcomas. We aimed to compare 99mTc-MIBI uptake and washout kinetics with the expression of Pgp and with chemotherapy response. Twenty-five patients (16 males and 9 females, aged between 8 and 65 years) with malignant musculoskeletal tumours were studied. After injection of 555-740 MBq 99mTc-MIBI, dynamic flow images of the involved area were obtained for 3 min, and planar images were acquired at 10 min and 1 h. From the dynamic images, a tumour perfusion index (TPI) was obtained using Patlak-Rutland analysis. Tumour to background (T/B) ratios of both early and delayed images and percent wash-out rate (WR%) of 99mTc-MIBI were calculated. Immunohistochemical analysis of Pgp was performed on biopsy specimens and the degree of expression was graded according to a semiquantitative scoring system, from 0 to 6. After neoadjuvant therapy, tumour response was assessed by examining the ratio of viable cells and by detecting percent necrosis. Scintigraphic results were compared with Pgp status and therapy response. Irrespective of the Pgp status, all patients showed significant perfusion and 99mTc-MIBI uptake in early images. There was not a significant correlation between T/B ratios of early and delayed images and Pgp expression. We observed a positive correlation between WR% and Pgp status (r=0.61, P<0.01), and the wash-out rate of 99mTc-MIBI was significantly higher in patients with high Pgp expression than in those with a low Pgp score (33% +/- 9% vs 17% +/- 9%). Therapy response was determined in 21 of 25 patients, and in only 5 of 21 cases was the percent necrosis more than 90%. Neither Pgp expression rate nor WR% was found to show a significant correlation with percent necrosis in the bulk tumour specimens. In conclusion, the initial uptake of 99mTc-MIBI in bone and soft tissue sarcomas did not correlate with Pgp expression. A relationship was found between the wash-out rate of 99mTc-MIBI and the Pgp score, with a significant difference in WR% being observed between patients with high and patients with low Pgp expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Endosonographic assessment of multimodality therapy predicts survival of esophageal carcinoma patients.

BACKGROUND: Standard endosonographic (EUS) staging criteria are unreliable for staging esophageal carcinoma after neoadjuvant therapy; however, measurement of tumor size reduction can identify patients who have achieved a pathologic response. In the current study the authors prospectively compared survival between patients classified as responders and those classified as nonresponders by EUS. METHODS: The maximal transverse cross-sectional area of the tumor was measured before and after neoadjuvant therapy in patients who were candidates for multimodality treatment. Response was defined as a > or = 50% reduction in tumor area. RESULTS: A total of 59 patients at 2 centers were followed for a median of 19 months. EUS assessed response in 34 patients (58%). Overall, responders had a median survival of 17.6 months compared with 14.5 months for nonresponders (P < 0.005). Survival was significantly longer in responders compared with nonresponders in the patient subgroup who underwent surgical resection (19.7 months vs. 14.6 months; P < 0. 005), the patient subgroup with adenocarcinoma (21.4 months vs. 10.8 months; P < 0.005), and the patient subgroup initially classified as having T3N1 disease (17.6 months vs. 14.1 months; P < 0.05). Survival was not found to differ significantly between responders and nonresponders in the subgroup of patients with squamous cell carcinoma. EUS response was the only clinical variable that was associated with survival time in a multivariate analysis (relative hazard = 0.27; P < 0.005). CONCLUSIONS: Patients with esophageal carcinoma who respond to neoadjuvant treatment as identified by EUS measurement of reduction in tumor size have a significantly better prognosis than nonresponders.

Adenocarcinoma↗

PubMedDate not supplied

Patient-reported acute gastrointestinal toxicity in men receiving 3-dimensional conformal radiation therapy for prostate cancer with or without neoadjuvant androgen suppression therapy.

OBJECTIVE: To investigate the impact of 2 months of neoadjuvant and 2 months of concurrent hormonal therapy on the acute gastrointestinal (GI) toxicities associated with 3-dimensional conformal radiation therapy (3D-CRT) for prostate adenocarcinoma. METHODS: The study cohort consisted of 80 men who underwent 3D-CRT with (n=40) or without (n=40) neoadjuvant and concurrent hormonal therapy. Computerized tomography-based planning occurred after neoadjuvant hormonal therapy. All patients completed a previously validated, quality-of-life self-assessment tool on 7 GI symptoms, including diarrhea, urgency, pain, rectal bleeding, cramping, mucus, and tenesmus, at baseline and weekly during radiation therapy. RESULTS: Patients who received hormonal therapy were more likely to have T2b, T2c, T3a, or T3b (P<0.001) or Gleason score 7, 8, or 9 (P=0.02) disease compared to those that did not. The dose delivered to the planning target volume was 70 Gy for both groups. Median radiation treatment volume was numerically smaller for the hormone group but not to a statistically significant degree (949 vs. 1043 cc, P=0.30). Patients who received hormonal therapy had less rectal pain (P<0.01) and tenesmus (P=0.02) but more rectal mucus (P=0.03) compared to those who did not. CONCLUSIONS: Prostate gland volume reduction after androgen suppression therapy may reduce patient-reported acute GI toxicities associated with 3D-CRT for prostate cancer.

Aged↗

PubMed2002

Effect of a short course of neoadjuvant hormonal therapy on the response to subsequent androgen suppression in prostate cancer patients with relapse after radiotherapy: a secondary analysis of the randomized protocol RTOG 86-10.

PURPOSE: To compare, by a secondary analysis, the therapeutic benefits of androgen suppression in protocol prostate cancer patients with relapse after radiotherapy (RT) for locally advanced disease who, in the Phase III trial beginning in 1987, were assigned to receive or not receive a short course of neoadjuvant maximal androgen suppression before definitive RT. METHODS AND MATERIALS: Between 1987 and 1991, 456 patients were entered in the Radiation Therapy Oncology Group trail 86-10 and randomized to receive (Arm I) or not to receive (Arm II) neoadjuvant hormonal therapy (HT), which was 4 months of goserelin (3.6 mg every 4 weeks) and flutamide (250 mg t.i.d.) before and during RT for bulky T2-T4 tumors. The overall and disease-specific survival after both randomization and salvage HT for patients with relapse was evaluated, as well as the duration of response in those patients undergoing salvage HT. The outcomes in patients who had received neoadjuvant HT vs. those who had not were compared. The median follow-up after randomization for all alive patients was 9.0 years and was 5.5 years for alive patients after beginning salvage HT. RESULTS: Fewer patients received salvage HT on Arm I than on Arm II (45% vs. 63%, p <0.001). The outcomes by randomized treatment arm (I vs. II) from the time of beginning salvage HT were similar. At 5 years after salvage HT, the overall survival rates were 41% and 41% and the disease-specific survival rates were 50% and 50%. At 8 years after randomization, the overall survival rates were 47% and 44% and the disease-specific survival rates were 55% and 56%. CONCLUSION: Although a 4-month course of neoadjuvant and concurrent maximum androgen suppression and RT (compared with RT alone) significantly increases the freedom from relapse rate and freedom from receiving salvage HT, it does not compromise the long-term beneficial effect of subsequent salvage HT, if needed for relapse. These findings with long follow-up in patients treated for locally advanced disease diagnosed 9-14 years previously should help allay concerns of the possible development of "resistance" to androgen suppression when 4-month courses of neoadjuvant HT are used before primary treatment.

Aged↗

PubMed1996

Biochemical and pathological effects of 8 months of neoadjuvant androgen withdrawal therapy before radical prostatectomy in patients with clinically confined prostate cancer.

PURPOSE: A prospective, nonrandomized trial was initiated to determine the duration of neoadjuvant therapy required for prostate specific antigen (PSA) to reach its nadir, evaluate the ability of an ultrasensitive assay to measure decreases in PSA less than 0.2 microgram./l., and characterize the effects of 8 months of neoadjuvant therapy on pathological stage, positive margin rates, proliferation and tumor marker immuno-staining. MATERIALS AND METHODS: We evaluated 50 patients with clinically localized prostate cancer treated by 8 months of reversible androgen ablation before radical prostatectomy. Serum PSA and testosterone levels were measured monthly. RESULTS: Serum PSA decreased by 84% after 1 month and by a further 52% between 3 and 8 months. Using an ultrasensitive assay, serum PSA decreased to undetectable levels (less than 0.1 microgram./l.) or reached its nadir in 22% of the cases after 3 months, 42% after 5 months and 84% after 8 months. Overall, the positive margin rate was 4%. Of the cases 68% were organ-confined and 24% were specimen-confined. The positive margin rate was not increased after reevaluation with cytokeratin, PSA and prostatic acid phosphatase immuno-staining but of 4 cases initially staged as P0 on hematoxylin and eosin evaluation 2 had microscopic foci of cancer with prostatic acid phosphatase staining. Immuno-staining with the proliferation markers proliferation cell nuclear antigen and Ki-67 showed decreased staining in surgical specimens relative to pretreatment needle biopsy specimens, which suggests that outgrowth of androgen independent clones does not develop during prolonged neoadjuvant therapy. CONCLUSIONS: Eight months of neoadjuvant androgen withdrawal therapy results in low positive margin rates and PSA nadir levels. The initial rapid decrease in PSA results from cessation of androgen regulated PSA synthesis and apoptosis, while the ongoing slower decrease reflects decreasing tumor volume.

Androgen Antagonists↗

PubMed2002

Primary chemotherapy in the treatment of breast cancer: the University of Texas M. D. Anderson Cancer Center experience.

The use of primary systemic (neoadjuvant) therapy has become widespread in the treatment of patients with locally advanced and operable breast cancer. The utilization of this therapeutic approach provides several advantages. By monitoring changes in the dimension of the tumor, efficacy can be evaluated or assessed in vivo; unnecessary toxicity can be avoided by allowing the physician to discontinue ineffective therapy. Furthermore, downstaging of a tumor through primary therapy may allow for breast-conserving surgery in patients with large operable breast cancer and render inoperable tumors resectable. Also, the use of primary therapy can provide a pathological complete response, which correlates with prolonged periods of remission. Treatment with FAC (5-fluorouracil/doxorubicin/cyclophosphamide) has proven to be effective as neoadjuvant therapy in locally advanced breast cancer in several trials. More recently, the integration of taxanes into primary therapy regimens has been explored with promising results. Studies have suggested that the use of primary therapy, particularly the use of FAC, should perhaps become the standard in patients with locally advanced disease. The history of clinical trials focusing on primary therapy in breast cancer at the M. D. Anderson Cancer Center will be reviewed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Preoperative chemoradiation for patients with locally advanced adenocarcinoma of the pancreas.

BACKGROUND: Improved resectability is a major theoretical benefit of preoperative chemoradiation for pancreatic cancer. Since 1994, patients at Duke University Medical Center with locally advanced pancreatic cancer have been treated with multimodality preoperative therapy. The purpose of this study was to review our experience with preoperative therapy for locally advanced pancreatic cancer and determine if an aggressive neoadjuvant regimen would not only downstage these tumors pathologically but also improve the odds of complete surgical resection. METHODS: The charts of 25 patients treated with neoadjuvant chemoradiation at Duke University Medical Center with biopsy-proven, locally advanced adenocarcinoma of the pancreas were reviewed. Tumors were defined as locally advanced based on radiographic or intraoperative evidence of disease that abuts the superior mesenteric artery or vein (n = 22) or involves lymph nodes that are within the proposed radiation field (n = 3). All 25 patients received external beam radiotherapy (median dose 4500 cGy) in daily fractions of 180 cGy over 5 weeks. All patients concurrently received 5-fluorouracil (FU), and many also received mitomycin C or cisplatin, or both. Patients were given a 3- to 4-week break before a restaging computed tomographic (CT) scan was performed. Three patients were not restaged: one died from metastatic disease; one was reclassified as having a neuroendocrine tumor; and one was lost to follow-up. RESULTS: On restaging after neoadjuvant therapy, 64% of patients had stable or decreased primary tumor size. Radiographically, two patients appeared potentially resectable, and seven others developed evidence of metastatic disease. Eight patients underwent exploration, but only five could be resected. Of the five patients resected, only one had negative margins and negative lymph nodes. This patient had significant pancreatitis on initial exploration. After neoadjuvant therapy, he had a complete response radiographically, and there was no residual cancer in his resection specimen. Pathologic examination of the other resection specimens suggested that despite significant tumor fibrosis, malignant cells persist even at the periphery of the lesions. CONCLUSION: Although neoadjuvant chemoradiation has many theoretical advantages in managing pancreatic malignancy, true pathologic downstaging of locally advanced lesions into tumors that can be removed with negative nodes and margins appears to be a rare event with currently used therapeutic regimens.

Adenocarcinoma↗

PubMed2001

Phase II trial of neoadjuvant estramustine and etoposide plus radical prostatectomy for locally advanced prostate cancer.

OBJECTIVES: To report the results of a Phase II trial of neoadjuvant estramustine and etoposide before radical prostatectomy in patients with locally advanced disease. METHODS: Treatment consisted of three cycles of estramustine (10 mg/kg/day) and etoposide (50 mg/m(2)/day) orally on days 1 through 21, repeated every 28 days, followed by radical prostatectomy. The eligibility criteria included locally advanced prostate cancer (clinical Stage T2b/c or T3, prostate-specific antigen [PSA] level of 15 ng/mL or greater, or Gleason score of 8 or higher) without evidence of metastatic disease. The median PSA level was 14 ng/mL (range 5.3 to 50), the median Gleason score was 7 (range 6 to 9), and 44% had Stage T2b/c or T3 disease. The primary endpoint was feasibility of neoadjuvant therapy and radical prostatectomy, including drug and surgery-related toxicities. Secondary endpoints included the pre-prostatectomy PSA level, local response, pathologic outcomes, and time to PSA failure. RESULTS: Eighteen patients were entered and completed all three cycles of therapy, and 16 (89%) underwent radical prostatectomy. A local response occurred in 15 (94%) of 16 patients with palpable tumors, and the serum PSA reached undetectable levels after therapy and before radical prostatectomy in 9 patients (50%). Five patients (28%) experienced grade 3 toxicity (two with deep venous thrombosis, two with neutropenia, and one with diarrhea) and one (6%) experienced grade 4 toxicity (pulmonary embolus) before surgery. The median operative time was 125 minutes, the mean blood loss was 665 mL, and the mean length of stay was 2.5 nights. Five minor surgical complications occurred in 4 patients. The pathologic analysis demonstrated residual carcinoma with squamous metaplasia and androgen deprivation effect in all patients. Five patients (31%) had organ-confined disease and 9 patients (56%) had specimen-confined disease. All patients achieved an undetectable PSA level postoperatively and at a median follow-up of 14 months (range 5 to 20) and without additional therapy, all 14 patients with negative lymph nodes were disease free. CONCLUSIONS: This trial confirms the feasibility of radical prostatectomy with acceptable surgical morbidity after neoadjuvant therapy with estramustine and etoposide in patients with locally advanced prostate cancer. However, this regimen is associated with estramustine-induced thromboembolic toxicity. The results of the pathologic analysis suggest a higher than expected rate of organ-confined and specimen-confined disease, but little histologic evidence of antitumor effect beyond that associated with androgen deprivation. Additional study of this paradigm with other drug regimens is warranted.

Antineoplastic Agents, Hormonal↗

PubMed1993

Stage I endometrial carcinoma: the role of neoadjuvant progesterone therapy.

A prospective study was devised in 1980 to assess the effect on survival of neoadjuvant Provera as part of the primary treatment of endometrial carcinoma in conjunction with surgery and radiotherapy. Between June 1980 and June 1985, 218 patients with Stage I adenocarcinoma of the corpus uteri were allocated on the basis of hospital of presentation to receive either neoadjuvant treatment with medroxyprogesterone acetate (MPA) 100 mg t.i.d. p.o. from diagnosis for 90 days, or no adjuvant treatment (the control group). The minimum follow-up was 5 years. There was no significant difference between the overall actuarial survival in the treatment group (123 cases) and that in the control group (95 cases). This was 83.7% and 69.2% at 5 and 10 years respectively in the treatment group and 78.9% and 70.7% in the control group (P > 0.1).

Adenocarcinoma↗