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Results for “Neoadjuvant therapy”

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PubMed1999

Immunohistochemical Analysis of Radical Prostatectomy Specimens After 8 Months of Neoadjuvant Hormonal Therapy.

Neoadjuvant hormone therapy (NHT) prior to radical prostatectomy (RP) results in residual foci of atrophic glands, which can be difficult to identify with hematoxylin-eosin staining, raising the possibility that the low positive-margin rates are an artifact of pathologic understaging. The purpose of this study was to evaluate changes in prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), as well as proliferation marker Ki-67 and Bcl-2 oncoprotein, by immunostaining after 8 months of NHT. Twenty-nine men with clinically confined prostate cancer who received 8 months of NHT and had both pretreatment biopsy and RP specimens obtained at Vancouver Hospital constituted the treatment group. The control group consisted of 23 RP specimens from patients not receiving NHT. Sections were stained with antibodies against PSA, PAP, proliferation marker Ki-67, and the antiapoptosis protein Bcl-2. The PSA and PAP immunostaining were graded for percentage of positive tumor cells and intensity of staining, while Ki-67 and Bcl-2 staining was graded according to the percentage of positive tumor cells. Absent or low percentage-positive PSA and PAP staining was observed in 40% to 50% of the NHT-treated RP specimens but none of the needle biopsy or untreated control RP specimens. Low-intensity PSA and PAP staining was detected only in RP specimens after NHT treatment, and then in only 20% of cases. Low or absent Ki-67 staining was noted in 78% of the NHT- treated RP specimens, compared with only 13% of the matched pre-NHT needle biopsies and 26% of untreated RP specimens. The percentage of specimens with high (>5%) Ki-67 staining decreased from 37% in the pre-NHT needle biopsies to 8% in the NHT-treated RP specimens. Bcl-2 staining increased after treatment with NHT, with 20% of the needle biopsies having high (>5%) Bcl-2 staining compared with 53% of the NHT-treated RP specimens. The frequency of low Bcl-2 staining (<1%) decreased from 53% in the pre-NHT needle biopsies to 27% in the NHT-treated RP specimens. Although PAP and PSA staining decreased after NHT, both markers remain sufficiently positive to be used as epithelial markers to help detect residual foci of prostate cancer that are difficult to identify on H&E-stained slides after NHT. Increased Bcl-2 after NHT, even in early-stage disease, is consistent with its role in the prevention of apoptosis and progression to androgen independence. Low levels of Ki-67 staining indicates a low probability of proliferation and outgrowth of androgen-independent clones after 8 months of NHT.

Journal Article↗

PubMed2000

p53 tumour-suppressor gene in non-small-cell lung cancer with neoadjuvant therapy.

In a phase II study for optimizing therapeutic management of locally advanced non-small-cell lung cancer the prognostic and therapeutic relevance of the p53 status was investigated. Biopsy or mediastinoscopy samples, collected prior to neoadjuvant chemoradiotherapy and corresponding resection specimens, were analysed immunohistochemically (CM1 antiserum) for p53 accumulation and molecular biologically (polymerase chain reaction/single-strand conformation polymorphism) for p53 mutations. The results were correlated to the response to therapy (regression grade) and to the survival times. p53 accumulation was found in 41.7% (prior to neoadjuvant therapy) and in 40.0% (after surgery) of the tumours. p53 mutation was demonstrated in 45.4% (prior to neoadjuvant therapy) and in 46.4% (after surgery) of the investigated tumours. Neither before nor after therapy was any correlation to the survival times or to the response to therapy seen in the collective analysed. Thus, such investigations are not suitable for identifying patients with locally advanced non-small-cell lung cancer who might benefit, to different extents, from neoadjuvant therapy.

Adult↗

PubMedDate not supplied

[Neoadjuvant therapy for localized osteosarcoma of extremities. Results from the Cooperative osteosarcoma study group COSS of 925 patients].

BACKGROUND: Owing to twenty years of multicentric interdisciplinary cooperation, the COSS group has been able to collect data on a large group of osteosarcoma patients treated by neoadjuvant therapy. This paper reviews results achieved in patients with localized extremity tumors. PATIENTS AND METHODS INCLUSION CRITERIA: Registration into a completed neoadjuvant COSS-Study. Histologically confirmed, primary, localized, high-grade, central osteosarcoma of an extremity; age < 40 years; no pretreatment; interval diagnosis to chemotherapy < or = 3 weeks; no severe comorbidity. Chemotherapy: HD-methotrexate +/- doxorubicin +/- cisplatin +/- ifosfamide +/- BCD. Scheduled local therapy: Surgery. RESULTS: 925 evaluable patients from 101 institutions. Median age 15 years, m:f 1.4:1. Primary site: femur 510, tibia 251, humerus 100, fibula 51, other 13. Tumor-size < 1/3 of the involved bone 616, > or = 1/3 304. Definitive surgery in 903/925 cases, 443 limb salvage procedures. Good response (> 90% necrosis) in 469/806 (58.2%) evaluated tumors. Median follow-up for surviving patients: 5.42 years. Actuarial survival after 5 and 10 years: 72.5% (95%-CI 69.3-75.7) and 66.3% (62.5-70.0), relapse-free 62.1% (58.7-65.4) and 59.4% (55.8-63.0). 683/925 alive (601 first remission), 242 deceased (212 tumor progression, 30 other causes). 66.2% (97.3%) of all relapses within 2 (5) years. Prognosis correlates with tumor-size (< vs. > or = 1/3: 69.9% vs. 58.3% at 10 years) and -site (tibia: 74.2%, humerus: 54.5%) and -response (good vs. poor: 78.2% vs. 52.5%) (all p < 0.01). Actuarial 10-year survival by response grading I-VI according to Salzer-Kuntschik 80.9%, 82.8%, 71.1%, 60.7%, 47.7%, 27.3%. COSS-studies with preoperative 4-drug therapy more efficacious than less aggressive protocols. No impact of doxorubicin scheduling (sequential: rapid vs. 48 h-continuous infusion) or cisplatin scheduling (randomized: 5 h vs. 72 h-infusion) on prognosis detected. CONCLUSIONS: Intensive multiagent chemotherapy and delayed surgery for localized extremity osteosarcoma led to excellent oncologic results in the COSS-studies. Tumor-size, -site, and -response as well as the intensity of upfront chemotherapy correlated with outcome. Giving doxorubicin and cisplatin by continuous infusions did not result in discernible prognostic disadvantages.

Adolescent↗

PubMed1989

Neoadjuvant therapy for locally invasive bladder cancer.

The present investigation was conducted to examine the effect of neoadjuvant PVB and CAP regimens for locally invasive bladder cancer and consisted of two studies: (1) a retrospective nonrandomized study of neoadjuvant PVB therapy, and (2) a well-controlled randomized study of neoadjuvant CAP therapy. A total of 25 patients with primary locally invasive bladder cancer were entered into the PVB study between January 1981 and December 1985. Since 1986, 31 patients have been randomized into the CAP study. In the PVB-treated group, a 71.4% complete response (CR) plus partial response (PR) rate and a 71.4% downstaging were noted. On the other hand, in the CAP-treated group, a 50.0% CR plus PR rate and a 88.9% downstaging were noted. The 2- and 5-year survival rates of neoadjuvant PVB were 78.6 and 60.6%, respectively. In contrast, the 2-year survival rate of the neoadjuvant CAP-treated group was 100% at a mean follow-up of 15.8 months. No statistical significance was achieved in the survival rates. These results indicated that neoadjuvant PVB and CAP would be useful in the management of invasive bladder cancer.

Aclarubicin↗

PubMed2004

Reduction in PSA messenger-RNA expression and clinical recurrence in patients with prostatic cancer undergoing neoadjuvant therapy before radical prostatectomy.

BACKGROUND: We assessed the incidence of micro-metastases at surgical margins (SM) and pelvic lymph nodes (LN) in patients submitted to radical retropubic prostatectomy (RP) after neoadjuvant therapy (NT) or to RP alone. We compared traditional staging to molecular detection of PSA using Taqman-based quantitative real-time PCR (qrt-PCR) never used before for this purpose. METHODS: 29 patients were assigned to NT plus RP (arm A) or RP alone (arm B). Pelvic LN were dissected for qrt-PCR analysis, together with right and left lateral SM. RESULTS: 64,3% patients of arm B and 26.6% of arm A had evidence of PSA mRNA expression in LN and/or SM. 17,2% patients, all of arm B, had biochemical recurrence. CONCLUSIONS: Qrt-PCR may be more sensitive, compared to conventional histology, in identifying presence of viable prostate carcinoma cells in SM and LN. Gene expression of PSA in surgical periprostatic samples might be considered as a novel and reliable indicator of minimal residual disease after NT.

Journal Article↗

PubMed1997

Thoracoscopic staging of IIIB non-small cell lung cancer before neoadjuvant therapy.

BACKGROUND: Bronchoscopy and imaging techniques are the most valuable tools for noninvasive staging of patients with locally advanced non-small cell lung cancer but their overall accuracy is not satisfactory. Neoadjuvant therapy protocols require strict criteria for patient selection and invasive staging should be carried out to establish standardized inclusion criteria and to homogenize posttreatment results. The aim of this prospective study was to evaluate the role of thoracoscopy in the assessment of the real extent of lung cancer in patients with the clinical suspicion of stage IIIB disease. METHODS: From January 1993 to March 1996, we observed 64 patients with suspected IIIB non-small cell lung cancer. Forty-three patients were considered eligible for this study and were divided into three groups: group I, cytologically negative pleural effusion (n = 10); group II, computed tomographic suspicion of mediastinal infiltration (n = 30); and group III, contralateral lymphadenopathy not accessible by mediastinoscopy (n = 3). RESULTS: No complications related to thoracoscopy occurred. Of 10 patients in group I, thoracoscopy up-staged the disease to IIIB in 6 (60%). Of 30 patients with suspicion of T4 (group II), thoracoscopy confirmed T4 in 15 patients (50%). Nine (30%) were downstaged to stage IIIA and 2 (6.6%) to stage II. In 4 patients (13.4%) thoracoscopy failed to yield definitive staging. In all 3 patients of group III, thoracoscopy confirmed stage IIIB. CONCLUSIONS: Thoracoscopy proved adequate for correct staging in 39 of 43 patients (91%); therefore, it should be considered in the staging work-up of suspected stage IIIB patients.

Adult↗

PubMed1993

Downstaging of localized prostate cancer by neoadjuvant therapy with flutamide and lupron: the first controlled and randomized trial.

Although the only opportunity to cure prostate cancer is treatment at an early stage, radical prostatectomy has remained relatively unpopular because 40-50% of prostate cancers estimated at diagnosis as confined to the prostate are found to be at a more advanced stage following histopathological analysis of the surgical specimen. This first prospective, randomized trial investigated the potential advantages of 3-month neoadjuvant combination therapy with flutamide and lupron before radical prostatectomy vs. prostatectomy alone in early stage prostate cancer. Cancer-positive margins were reduced from 38.5% (25 of 65) in control patients to only 13.0% (10 of 77) in men who received neoadjuvant combination therapy with the antiandrogen flutamide and the luteinizing hormone-releasing hormone (LHRH) super-agonist Lupron before radical prostatectomy (p = 0.006). Moreover, comparison of the final stage determined by histopathological examination of the surgical specimen with that estimated at diagnosis showed that a more advanced stage (upstaging) was found in 53.8% of controls, but patients who received combination therapy had an opposite effect: a more favorable stage than expected at diagnosis was found in 23.4% of cases (downstaging), a 77.2% advantage of neoadjuvant combination therapy. The concern about radical prostatectomy, underestimation of stage, is thus markedly improved by 3-month neoadjuvant therapy with flutamide and a LHRH superagonist. Cancer-negative margins are expected to be accompanied by a life expectancy not different from that of men of similar age with no prostate cancer; therefore, the present data, combined with efficient detection of early stage prostate cancer, offer the basis for dramatic improvement in the morbidity and mortality of prostate cancer.

Adenocarcinoma↗

PubMed1993

Neoadjuvant therapy for unresectable pancreatic adenocarcinoma.

The purposes of this study were to determine whether continuous infusion of fluorouracil combined with external-beam radiation therapy improved the resectability and survival of patients with pancreatic carcinoma. Sixteen patients with unresectable disease confined to the pancreas and celiac nodes were treated, and their outcome was compared with that of 24 patients with potentially resectable disease who were treated concurrently. The neoadjuvant therapy was completed with acceptably few toxic effects but with only a minor decrease in tumor size. Two patients underwent resection and remained free of disease 20 and 22.5 months later. However, the median survival of the entire neoadjuvant group was 8 months. All 24 patients with potentially resectable carcinoma underwent surgical exploration. Fifteen of the 24 patients underwent resection and survived a median of 12.5 months. Neoadjuvant chemoradiation may have improved outcome and resectability for two (12.5%) of 16 patients with unresectable pancreatic carcinoma, but more effective therapy options must be developed to improve outcome.

Adenocarcinoma↗

PubMed1998

Neoadjuvant therapy in localized prostate cancer before surgery and radiotherapy.

Neoadjuvant hormonal therapy brings the possibility of improving the results of radical treatment of clinically localized prostate cancer. While the advantages of this therapy combined with radiotherapy and cryosurgery are encouraging, as yet the positive effects of initial hormonal ablation before radical prostatectomy are still not proven.

Journal Article↗

PubMed1991

Neoadjuvant therapy in invasive bladder cancer. Problems and pitfalls.

It is clear that some transitional-cell tumors of the bladder will respond to combined therapy. However, in the absence of randomized controlled trials, the impact of repeated transurethral resections versus the effect of chemotherapy cannot be assessed adequately, and such trials are urgently needed before neoadjuvant therapy can be considered standard. In addition, newer chemotherapy agents or the combination of currently available drugs with the addition of hematopoietic growth factors such as granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor to reduce toxicity and permit dose intensification in an attempt to increase overall response rates offer fruitful avenues for clinical research. Although cisplatin-based chemotherapy obviously does not have the same impact on bladder cancer that it does on testicular cancer, the initial results are encouraging. The "wall" has been breached, and the demonstration that urothelial tumors can be added to the list of chemotherapeutically responsive tumors should encourage urologic, radiologic, and medical oncologists to combine efforts in randomized, controlled studies of integrated approaches to therapy.

Combined Modality Therapy↗

PubMed1998

[Adjuvant and neoadjuvant therapy of rectal carcinoma. The current status].

BACKGROUND: The Consensus Conference of the German Cancer Society (CAO/AIO/ARO, 1.7.1998) has recently updated recommendations for patients with rectal cancer. Instead of a former reservation regarding the indication of adjuvant therapy for rectal cancer the actual version of the consensus particularly emphasizes the role of postoperative radiochemotherapy for stage-II/III tumors. This article reviews the most recent and ongoing trials of adjuvant and neoadjuvant therapy of rectal cancer. RESULTS: To avoid local recurrence is the most important aspect in the primary treatment of rectal cancer. In some series, e.g. the results of the Surgical Department of the University of Erlangen, a significant correlation between local control and survival was noted. The final results of the Swedish Rectal Cancer Trial with 1168 randomized patients not only confirmed the potential of radiotherapy to reduce local recurrence rate, but also demonstrated a significant survival advantage for patients receiving short-course preoperative radiation therapy. Postoperative combination therapy is usual in the United States and in most European countries since the publication of two randomized trials of the Gastrointestinal Tumor Study Group (GITSG) and the North Central Cancer Treatment Group (NCCTG). The survival advantage resulting from an adjuvant radiotherapy with conventional doses and concurrent fluorouracil-based chemotherapy as compared to surgery alone was recently confirmed in a Norwegian trial. Protracted venous 5-fluorouracil infusion should further improve treatment results. Numerous phase-II studies have demonstrated the efficacy of preoperative radiochemotherapy with high rates of pathological response. Thus, neoadjuvant radiochemotherapy is recommended for patients with locally advanced tumor primarily not amenable to curative surgery. Prospective randomized trials are ongoing to clarify the role of preoperative versus postoperative combined treatment for patients with resectable rectal cancer. CONCLUSION: Radiochemotherapy for rectal cancer is recommended as standard treatment outside clinical trials for stage II/III patients after curative treatment and for patients with T4-tumor prior to surgery. The optimal use of chemotherapy and the sequence of treatment modalities remains to be elucidated.

Carcinoma↗

PubMed2000

[Evaluation of neoadjuvant therapy in breast carcinoma].

For 20 years preoperative chemotherapy has been the treatment of choice in inflammatory breast cancer. Adjuvant chemotherapy does not show any advantages over neoadjuvant systemic chemotherapy in terms of survival of patients with breast cancer. Reduction of the size of the tumor enables the surgeon to perform more breast-conserving surgery, but the long-term results for breast tumor to recur in these patients are not yet available. At our hospital, a tumor larger than 30 mm is an indication for mastectomy. In general, only 20.6% of all patients are suitable for neoadjuvant chemotherapy. Patients with lobular carcinoma or with tumors with an extensive ductal carcinoma in situ part will not benefit from such therapy. Tumor remission following neoadjuvant chemotherapy is of prognostic relevance. The rapid therapeutic effect of neoadjuvant therapy allows short-term evaluation of this treatment.

Breast Neoplasms↗

PubMed1987

Neoadjuvant therapy for advanced head and neck cancer with allopurinol-modulated high dose 5-fluorouracil and cisplatin. A phase I-II study.

The combination of cisplatin (100 mg/m2) and 5-fluorouracil (5-FU) by continuous infusion (1 g/m2/day for 5 days) has been reported to produce a high response rate as neoadjuvant therapy for advanced squamous cell head and neck cancer. We sought to improve the response rate by increasing the dose of 5-FU to 1.5 g/m2/day and 2.0 g/m2/day with allopurinol modulation to reduce toxicity. The overall response rate in the 30 patients who received three courses of chemotherapy was 100% with a 50% complete response (CR) rate. A 50% CR rate was observed in patients with T3 (six of 12) and N3 (four of eight) disease. Six patients (four with CR) did not complete subsequent treatment as planned. Seven of 11 (63.6%) chemotherapy complete responders and three of 12 (25%) partial responders (one lost to follow-up) who received all planned treatment are free of disease. The major toxicity encountered was stomatitis (severe in 32%) followed by leukopenia. The maximum tolerated dose of 5-FU in this combination with allopurinol protection was 1.5 g/m2/day. Cisplatin plus high dose 5-FU does not appear to be associated with a higher CR rate than that reported with conventional doses of 5-FU and is more toxic.

Adult↗

PubMed1994

MR mammography with pharmacokinetic mapping for monitoring of breast cancer treatment during neoadjuvant therapy.

The increased clinical understanding of neovascularization and its changes during therapy are the basis for therapy-response monitoring with MR mammography of breast cancer treatment. With dynamic MR imaging, objective quantification of neovascularization can be achieved using pharmacokinetic analysis of contrast media enhancement. This technique likely will be of major clinical importance for the noninvasive evaluation of neoadjuvant therapy with a favorable cost-benefit ratio.

Adult↗

PubMed2003

Section IV: selective use of neoadjuvant therapy.

Compared to lung cancer, treatment algorithms for esophageal cancer are not well established as a consequence of the low incidence of esophageal malignancies. Radiation therapy and chemotherapy as single modality therapies are inadequate for a reliable cure. Current debate in the literature focuses on the potential added value of neoadjuvant chemoradiation therapy prior to surgery versus surgery alone. We believe this debate is secondary to the lack of careful discrimination with respect to staging of high-risk groups. We advocate the selective use of neoadjuvant chemoradiation therapy for localized esophageal cancer, similar to its use in stage IIIA (N2) NSCLC, and justify this approach on the basis of our own single institution data, which is summarized in this article.

Chemotherapy, Adjuvant↗

PubMed2001

Immunohistochemical and clinicopathologic analysis of response to neoadjuvant therapy for esophageal squamous cell carcinoma.

Recently, neoadjuvant chemotherapy combined with radiation (NAT) has been used in the active treatment of progressive esophageal cancer (T4). However, many patients are resistant to supplemental therapy, and it is necessary to to be aware that side-effects may occur. Accordingly, to minimize adverse reactions and cost, it is important to determine the indications for NAT. We investigated 34 patients with T4 esophageal squamous cell carcinoma and examined the relation between the effects of NAT and immunohistochemical or additional clinicopathologic factors. There was no relation between clinicopathologic factors and immunohistochemical findings (p53 or hsp27 expression), and no clinicopathologic factors showed a relation to a supplemental therapeutic effect. In addition, there was no correlation between p53 staining and therapeutic effects (P=0.734). In contrast, there was a correlation (P=0.0058) between hsp27 staining and therapeutic effect. In conclusion, the usefulness of hsp27 immunostaining in predicting the therapeutic effect of NAT was confirmed in T4 esophageal squamous cell carcinoma.

Adult↗

PubMed2004

Paclitaxel: as adjuvant or neoadjuvant therapy in early breast cancer.

Paclitaxel is a antimicrotubule agent with established antitumour activity in a variety of cancers including breast cancer. The efficacy of intravenous paclitaxel as adjuvant therapy for early breast cancer has been investigated in two large, randomised trials; it was administered sequentially to standard doxorubicin-cyclophosphamide (AC) combination therapy and compared with cycles of AC alone. In both trials, the addition of sequentially administered paclitaxel to the AC regimen significantly improved disease-free survival at 5 years compared with AC alone. In one of the trials, women who received paclitaxel also had a significant improvement in overall 5-year survival time. In randomised trials of neoadjuvant therapy for women with early breast cancer, paclitaxel or paclitaxel-containing regimens showed efficacy in terms of response/remission rates, local breast tumour recurrence and proportion of patients eligible for breast-conserving surgery. The most frequently reported grade 3-4 adverse events with paclitaxel administered sequentially to AC were haematological events (neutropenia, thrombocytopenia, anaemia) and nausea/vomiting.

Antineoplastic Agents, Phytogenic↗

PubMed1992

Interferon modulation of 5-fluorouracil: use in neoadjuvant therapy inhibits experimental liver metastases in nude mice.

Experimental liver metastasis was studied in 4-5 week old athymic nude mice that were injected intrasplenically with a human colorectal tumor cell line (LoVo). A treatment schedule combining 5-fluorouracil and interferon (IFN) was previously shown to inhibit liver metastases. When this treatment was delayed until after splenectomy at 1, 2 and 3 weeks after tumor cell injections, liver metastases were not inhibited. However, when IFN was given during the interval between tumor cell injections and splenectomy (as neoadjuvant therapy), liver metastases were inhibited in the 2 and 3 week groups, but not in the 1 week group.

Animals↗