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PubMed1999

Correlation between EGFR and c-erbB-2 oncoprotein status and response to neoadjuvant chemotherapy in cervical carcinoma.

Neoadjuvant chemotherapy prior to definitive radical surgery or radiotherapy may be effective in reducing tumor volume or clinical stage and may even enhance pelvic control and survival. However, there are significant limitations to the use of neoadjuvant therapy in the non-responder group. They include delayed total treatment course, the presence of drug resistant clones which result in accelerated tumor growth, and limited bone marrow reserve for subsequent definitive therapy. Thus, there is a need to identify parameters providing a more precise indication of the response to neoadjuvant chemotherapy in patients with invasive cervical cancer. From Jan. 1995 to Jan. 1996, neoadjuvant chemotherapy with 3 courses of cisplatin and vincristine was used in 32 patients with invasive cervical cancer (FIGO stage Ib to IIIb; tumor size greater than 2 cm). Prior to chemotherapy, quantitative tissue levels of epidermal growth factor receptor (EGFR) and c-erbB-2 oncogene protein were measured by using an enzyme-linked immunosorbent assay (ELISA). Tumor size was estimated before and after chemotherapy. Relations between oncoproteins and reductions of tumor size were evaluated. Tumor size prior to neoadjuvant chemotherapy did not show any correlation with either the concentrations of EGFR or c-erbB-2 oncoprotein. As well, the tumor reduction index did not manifest any correlation with EGFR, it did had an inverse linear correlation with the c-erbB-2 oncoprotein levels (Rs = -0.71, P < 0.05). The results of this study suggest that c-erbB-2 oncoprotein is associated with a reduced response to neoadjuvant chemotherapy in primary treatment of invasive cervical cancer and may be useful in directing therapeutic approaches.

Adult↗
PubMed1995

Changing pattern of relapse in osteosarcoma of the extremities treated with adjuvant and neoadjuvant chemotherapy.

In 551 patients with osteosarcoma of the extremities treated between 1980 and 1991 in our Institution with surgery only (35 cases), surgery combined with adjuvant chemotherapy (147 cases) or neoadjuvant chemotherapy (369 cases) the relapse patterns were analyzed. Adjuvant chemotherapy was performed according to 2 different protocols and neoadjuvant chemotherapy according to 3 different protocols successively activated. In the 252 patients who relapsed, the interval between initial treatment and first relapse was significantly longer in the group treated with adjuvant and neoadjuvant chemotherapy (18.1 and 21.3 mo) than in the group treated with surgery only (5.4 mo). For patients treated with neoadjuvant chemotherapy, a longer interval was seen in the most effective regimen of neoadjuvant chemotherapy (25 mo). No significant differences were seen among the 3 groups, according to the site of first metastasis, although in patients treated with the most effective neoadjuvant regimen there was a higher incidence of bone metastasis. In patients who relapsed with pulmonary metastases the average number of nodules seen by standard X-rays, as well as CT scans, was significantly higher in patients treated with surgery only (3.6) than in patients treated with adjuvant or neoadjuvant chemotherapy (2.5 and 2.6 nodules). We conclude that these changes in metastatic pattern in patients treated with adjuvant and neoadjuvant chemotherapy are important, because they may encourage the use of salvage therapy with thoracotomy in a larger number of patients. Prolongation of time relapsed after more effective regimens of adjuvant and neoadjuvant chemotherapy should be considered when evaluating the preliminary results of new chemotherapy protocols.

Adult↗
PubMed2002

Current approaches of neoadjuvant chemotherapy in cervical cancer.

Despite remarkable improvement in clinical management, the survival of cervical cancer patients has shown only minor progress in the last decade, particularly in patients with advanced and high-risk disease. Multimodal treatment option has been investigated, such as the concurrent use of chemotherapy and radiation, neoadjuvant chemotherapy and radical hysterectomy, or neoadjuvant chemotherapy followed by radiotherapy. Recently, a flow of randomized clinical trials have demonstrated a benefit from the concurrent chemoradiation for the treatment of the cancer of the cervix. This review will summarize the role and benefit of neoadjuvant chemotherapy in combination with sequential or concurrent radiotherapy and radical surgery for treatment of cervical cancer.

Chemotherapy, Adjuvant↗
PubMed2002

The role of neoadjuvant chemotherapy for breast cancer treatment.

Neoadjuvant chemotherapy has become popular, especially for patients with advanced breast cancer. The pros and cons of neoadjuvant chemotherapy for treating breast cancer patients are reviewed. The advantages of neoadjuvant chemotherapy are 1) overall survival and recurrence-free survival rate are the same as post-operative chemotherapy, 2) serves as an in vivo sensitivity test, 3) increases the rate of breast conserving therapy, 4) facilitates the study of cancer biology. On the other hand, the disadvantages of neoadjuvant chemotherapy are 1) it modifies the stage, 2) treatment delay of PD cases, 3) residual intraductal component may be left behind after breast conserving surgery, 4) there are some cases of over-treatment. Combination chemotherapy is one possible way to increase the pathological CR rate, although the optimal order and cycles have not been determined. To avoid residual cancer cells after breast conserving surgery, the shrinkage pattern should be evaluated by MRI. Core needle biopsy should be performed before neoadjuvant chemotherapy to avoid over-treatment. It is essential to develop more effective regimens and stratify patients based on predictive factors.

Antineoplastic Agents↗
PubMed2005

Association of pretherapeutic expression of chemotherapy-related genes with response to neoadjuvant chemotherapy in Barrett carcinoma.

PURPOSE: We analyzed pretherapeutic gene expression patterns of patients with locally advanced adenocarcinomas of the esophagus with regard to response to neoadjuvant chemotherapy. EXPERIMENTAL DESIGN: Pretherapeutic, paraffin-embedded, formalin-fixed endoscopic esophageal tumor biopsies of 38 patients with locally advanced esophageal adenocarcinomas (Barrett adenocarcinoma) were included. All patients underwent two cycles of cisplatin and 5-fluorouracil (5-FU) therapy with or without additional paclitaxel followed by abdominothoracal esophagectomy. RNA expression levels of 5-FU metabolism-associated genes thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase, MAP7, and ELF3, of platinum- and taxane-related genes caldesmon, ERCC1, ERCC4, HER-2/neu, and GADD45, and of multidrug resistance gene MRP1 were determined using real-time reverse transcriptase-PCR. Expression levels were correlated with response to chemotherapy, histopathologically assessed in surgically resected specimens. RESULTS: Responding patients showed significantly higher pretherapeutic expression levels of MTHFR (P = 0.012), caldesmon (P = 0.016), and MRP1 (P = 0.007). In addition, patients with high pretherapeutic MTHFR and MRP1 levels had a survival benefit after surgery (P = 0.013 and P = 0.015, respectively). Additionally, investigation of intratumoral heterogeneity of gene expression of relevant genes (MTHFR, caldesmon, HER-2/neu, ERCC4, and MRP1), verified in nine untreated Barrett adenocarcinomas by examination of five distinct tumor areas, revealed no significant heterogeneity in gene expression indicating that expression profiles obtained from biopsy material may yield a representative genetic expression profile of total tumor tissue. CONCLUSIONS: Our results indicate that determination of mRNA levels of few genes may be useful for the prediction of the success of neoadjuvant chemotherapy in individual cancer patients with locally advanced Barrett adenocarcinoma.

Adenocarcinoma↗
PubMed1999

The role of docetaxel (Taxotere) in neoadjuvant chemotherapy of breast cancer.

Neoadjuvant chemotherapy has become standard therapy in the management of breast cancer patients with locally advanced disease with inoperable tumors and inflammatory breast cancer. Patients with earlier stage breast cancer and operable tumors may also benefit from treatment with neoadjuvant chemotherapy. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) is thought to be one of the most potent agents in the treatment of metastatic breast cancer and is therefore being investigated for its likely benefit in preoperative, neoadjuvant regimens. Several large phase II and randomized phase III trials are evaluating docetaxel as a single agent, in combination, and/or sequentially in the preoperative setting. Preliminary findings demonstrate high complete and partial response rates and a tolerable toxicity profile. These results are consistent with the view that incorporation of docetaxel in neoadjuvant chemotherapy regimens will contribute to improved patient outcome. Ongoing studies will provide important information regarding the most appropriate regimens and schedules of docetaxel to use in the preoperative, neoadjuvant setting.

Anthracyclines↗
PubMedDate not supplied

Do the conventional clinicopathologic parameters predict for response and survival in head and neck cancer patients undergoing neoadjuvant chemotherapy?

AIMS AND BACKGROUND: Neoadjuvant chemotherapy for head and neck carcinoma is still an important treatment modality. The prognostic value of patient and tumor parameters has been extensively evaluated in several trials, yielding mixed results. We report the prognostic factors emerging from a group of patients undergoing neoadjuvant chemotherapy. PATIENTS AND METHODS: From April 1986 to June 1992, 149 consecutive patients received cisplatin-5-fluorouracil-based neoadjuvant chemotherapy. After four courses of chemotherapy, patients underwent local-regional treatment with surgery, radiation or both. A variety of patient and tumor characteristics were evaluated as predictors for response to chemotherapy and survival. RESULTS: The complete response, partial response and no response rates to NAC were 52%, 33% and 15%, respectively. No parameters predicted response to chemotherapy. At a maximum follow-up of 87 months, overall survival was 39% and disease-free survival was 49%. Variables shown to be predictors of survival in univariate analyses were age, performance status, histology, site, T, N, stage, and response to chemotherapy. Using the Cox regression analysis, only complete response to induction chemotherapy (P = 0.0006), performance status (P = 0.03), stage (P = 0.01), age (P = 0.03) and primary tumor site (P = 0.04) emerged as independent prognostic factors for survival. CONCLUSIONS: Complete response to chemotherapy was confirmed as the strongest prognostic factor influencing survival. However, conventional clinicopathologic factors did not predict response, hence, potential prognostic biologic and molecular factors for response must be sought. At present, much effort must be made for the improvement of the complete response rate, which seems to be a requisite to prolong survival.

Adult↗
PubMed2005

Neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Neoadjuvant chemotherapy for breast cancer was originally used in locally advanced inoperable disease in order to achieve surgical resection. It was then extended to operable breast cancer with a view to downstaging tumours to facilitate breast-conserving surgery. Increasingly, it is being considered as a treatment for earlier-stage disease. METHODS: A Medline literature search was performed to identify articles relating to neoadjuvant chemotherapy in breast cancer published in the English language between 1960 and 2004. Secondary references were obtained from key articles. Search words included 'neoadjuvant chemotherapy', 'breast cancer', 'tumour biology', 'tumour markers' and 'sentinel lymph node biopsy'. RESULTS: Long-term results from randomized studies have shown no difference in disease-free or overall survival between neoadjuvant and adjuvant chemotherapy. The main benefit of neoadjuvant chemotherapy is its ability to downstage large tumours with a view to treatment by breast-conserving surgery, although there is a non-significant increase in the local recurrence rate. Initial results of neoadjuvant chemotherapy trials using newer agents such as taxanes have demonstrated a greater pathological complete response. Whether this will translate into better long-term survival remains to be seen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Neoadjuvant chemotherapy in gynecological cancers.

Neoadjuvant chemotherapy in gynecological cancers is an approach that is shown to have positive effects on survival. It increases the rate of resectability in ovarian and cervical cancers and thus contributes to survival. However, there are studies reporting that despite increasing operability, the approach does not make any changes in terms of survival. Nevertheless, no negative effects have been reported in studies conducted till today. Prospective and randomized well-designed studies that encompass a high number of cases and parameters, including cost-effectiveness, are needed in both types of cancers. Until the results of such studies are obtained, neoadjuvant chemotherapy may be taken into consideration as an alternative when conventional methods do not suffice. The number of studies concerning endometrial, vulvar and vaginal cancers are few in the area of neoadjuvant chemotherapy.

Adult↗
PubMed2005

A comparison of sentinel node biopsy before and after neoadjuvant chemotherapy: timing is important.

BACKGROUND: Because neoadjuvant chemotherapy is being used more frequently, the optimal timing of sentinel node biopsy (SNB) remains controversial. We previously evaluated the predictive value of SNB before neoadjuvant chemotherapy in clinically node-negative breast cancer. Our identification rate of the sentinel node among 52 patients before chemotherapy with a mean tumor size of 4 cm was 100%. In this study, we compared the identification rates of SNB before and after neoadjuvant chemotherapy and evaluated the false-negative rate of SNB after chemotherapy. METHODS: A retrospective institutional database review identified 36 women who underwent SNB after neoadjuvant chemotherapy for breast cancer from 1999 to 2004. The initial clinical tumor size and lymph node status, SNB pathology, axillary lymph node dissection pathology, and residual pathologic tumor size were reviewed. RESULTS: Sixteen of 36 patients had a clinically negative axilla before neoadjuvant therapy. SNB after neoadjuvant therapy was successful in 29 patients (80.6%), although 7 patients did not map (19.4%). Six of the 7 patients who failed to map had a clinically positive axilla initially. Axillary disease was found in 6 of 7 of these patients at dissection (85.7%). Of the 29 patients who mapped successfully, 13 (45%) were SNB negative, and 16 (55%) were SNB positive. Of the 13 SNB-negative patients, 2 had a positive axillary lymph node dissection, yielding a false-negative rate of 11%. Thirteen patients who mapped had a clinically positive axilla before therapy (45%). Of the 11 patients with true-negative SNBs, 7 (64%) were clinically node negative at presentation. The initial tumor sizes on examination ranged from 2 to 9 cm (mean, 5.0 cm), and residual pathologic tumor sizes ranged from 0 to 6 cm (mean, 1.8 cm). Failure to map correlated with a clinically positive axilla at presentation (100% vs 45%) but did not correlate with initial tumor size. CONCLUSIONS: Sentinel node identification rates are significantly better when mapping is performed before neoadjuvant chemotherapy (100% vs 80.6%), with failure to map correlated with clinically positive nodal disease at presentation and residual disease at axillary lymph node dissection. Among patients who map successfully after chemotherapy, the false-negative rate is high (11%). Given these findings, we currently recommend SNB before neoadjuvant chemotherapy for clinically node-negative patients, and raise concerns about the use of SNB after neoadjuvant therapy in patients with an initially clinically positive axilla.

Antineoplastic Agents↗
PubMed1996

Concomitant and neoadjuvant chemotherapy in conjunction with radiotherapy in the management of locally advanced cervical cancer.

Radiotherapy is standard treatment for women with locally advanced cervical cancer (stage IIB-IVA). Radiotherapy fails to control disease progression within the irradiated field in more than 40% of patients. The disease bulk is a major factor limiting the curative probability of pelvic radiotherapy. Chemotherapy has been integrated with pelvic radiotherapy with the goal of improving local tumor control and treating microscopic metastases outside the radiotherapy field. Simultaneous chemotherapy and radiotherapy, neoadjuvant chemotherapy followed by radiotherapy, and adjuvant chemotherapy after radiotherapy, have been investigated. Hydroxyurea during pelvic radiotherapy has been reported to be associated with an improved progression-free (P = .05) and survival (P = .066) advantage. Several randomized trials of concomitant radiotherapy with fluorouracil, mitomycin, or cisplatin have been completed, but no results are published. Neoadjuvant chemotherapy with cisplatin-containing regimens followed by radiotherapy has been studied in several randomized trials. Although tumor response after chemotherapy is reported in more than 50% of patients, no improvement in local disease control or in survival has been noted overall. In one large trial, neoadjuvant chemotherapy was inferior to standard pelvic radiotherapy in terms of local control and survival. Adjuvant chemotherapy after radiotherapy has been little studied, and no randomized trials have been reported. The results of trials in progress or completed but not yet reported will determine further clinical research directions. Chemotherapy during and after pelvic radiation therapy has been little studied.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Postoperative complications in patients of esophageal cancer after neoadjuvant chemotherapy.

We examined the effects of neoadjuvant chemotherapy on surgery by evaluating postoperative complications in 50 patients who had undergone neoadjuvant chemotherapy (Group A) and in 108 patients who had undergone surgery without neoadjuvant chemotherapy (Group B). Toxicity of grade 3 by chemotherapy were WBC in 3 patients (6%), alopecia in 3 patients (6%), and anorexia in 22 patients (44%). There were 4 patients with anastomotic leakage (8%) (all in minor), 5 patients with infection of wound (10%), 6 patients with arrhythmia (12%), no patients with postoperative bleeding, 2 patients with respiratory complications (4%), and no patients who died due to complications in Group A. In Group B, there were 13 patients with anastomotic leakage (13%) (all in minor), 12 patients with infection of the wound (11%), 11 patients with arrhythmia (10%), 2 patients with postoperative bleeding (2%), 8 patients with respiratory complications (7%), and 2 patients who died due to complications (2%). There was no significant difference in the incidence of postoperative complications between the patients who had undergone surgery after neoadjuvant chemotherapy, such as CDDP + 5FU therapy and FAP therapy, and the patients who had undergone surgery without neoadjuvant chemotherapy, in patients who had been diagnosed as being able to undergo relative non-curative resection or better, who had Ccr 60 ml/min or more and no severe complication, and whose stomach could be used for reconstruction of the esophagus, on the condition that surgery would be performed on NC patients at the end of first-course treatment.

Alopecia↗
PubMedDate not supplied

The potential role of neoadjuvant chemotherapy in advanced ovarian cancer.

There is a multitude of evidence from retrospective analyses and meta-analyses showing that the amount of residual tumor after debulking surgery and before chemotherapy is one of the most powerful prognostic determinants in advanced ovarian cancer. This supports the important role of maximum cytoreductive surgery as one of the cornerstones in the treatment of this disease. These same analyses, however, do not suggest that patients whose tumors cannot be debulked optimally derive a significant survival benefit from upfront surgery. For these patients and those who have a poor performance status or other morbidity, making comprehensive upfront surgery contraindicated, different therapeutic approaches have to be explored. One possible way to go is to change the timing of the different therapeutic modalities: upfront chemical cytoreduction, followed by a maximal surgical effort, in turn followed by the remainder of the first-line chemotherapy or neoadjuvant chemotherapy and interval or delayed debulking surgery. The potential role of this approach and the experience with it thus far are discussed.

Clinical Trials as Topic↗
PubMedDate not supplied

Future prospects of neoadjuvant chemotherapy in treatment of primary breast cancer.

Neoadjuvant chemotherapy in breast cancer was developed in the 1970s and is now used in patients with locally advanced or early resectable breast cancer. Early administration of systemic chemotherapy before local treatment in locally advanced breast cancer and early resectable breast cancer is intended to downstage the primary tumor to make subsequent local treatment (surgery/or radiotherapy) easier and, it is hoped, to eliminate occult distant micrometastases to prolong survival. Despite the theoretical and experimental data indicating the survival superiority of neoadjuvant chemotherapy over postoperative adjuvant chemotherapy, the role of neoadjuvant chemotherapy in treatment of breast cancer remains unclear. But for the effect of down-staging the primary tumor is confirmed, 60-80% of patients with resectable breast cancer can be treated by a breast conservation procedure after neoadjuvant chemotherapy. Large randomized clinical trials are needed to evaluate the survival benefit for neoadjuvant chemotherapy. The detection of clinical and new biological markers will be studied to select the nonresponders of neoadjuvant chemotherapy for alternative treatment approaches.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

18F-FDG PET and 99mTc-sestamibi scintimammography for monitoring breast cancer response to neoadjuvant chemotherapy: a comparative study.

Presurgical neoadjuvant chemotherapy has shown promise in the treatment of locally advanced breast carcinoma (LABC). Response assessment by clinical examination and mammography is difficult. This study evaluated and compared fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and technetium-99m sestamibi scintimammography (SMM) as potential methods for the early assessment of tumour response to neoadjuvant chemotherapy in patients with LABC. Seven patients underwent PET and SMM [planar and single-photon emission tomography (SPET)] before beginning chemotherapy, after the first and second cycles of chemotherapy and after completing chemotherapy prior to surgery. PET and SMM results were evaluated visually and semi-quantitatively by calculating standardised uptake values (SUV) and tumour/lung ratios in the initial and subsequent studies. The findings were correlated with the initial clinical and mammographic findings and the final histopathological diagnoses. There was a highly significant correlation between SUVmean, SUVmax and the tumour/lung ratio determined with SMM-SPET in the studies performed before and during neoadjuvant chemotherapy. All three patients with complete remission showed decreasing FDG and sestamibi uptake as early as 8 days after therapy. In the presurgical study, increased sestamibi and FDG uptake was no longer evident. Three patients had partial remission with clearly reduced but persisting focal FDG and sestamibi uptake after neoadjuvant therapy. One patient who did not respond to therapy had unchanged intense tracer uptake during chemotherapy that was evident with both techniques. An early decline in glucose metabolism or sestamibi uptake 8 days after beginning therapy did not necessarily predict complete tumour remission in the further course of chemotherapy. On the other hand, increased tracer uptake after the first cycle did not exclude a partial tumour response. After the second chemotherapeutic cycle both techniques were able to distinguish between complete and partial/no response. There was a good correlation between preoperative FDG and sestamibi uptake and the histopathologically determined tumour size. However, small residual invasive tumours in patients with clinically complete remission could not be visualised with either technique. The preliminary data demonstrate that sestamibi SMM is as useful as FDG-PET for the monitoring of tumour response to neoadjuvant chemotherapy.

Adult↗
PubMed1994

[Evaluation of combination chemotherapy for advanced gastric carcinoma as a neoadjuvant chemotherapy with CDDP, MMC, etoposide and 5'-DFUR].

Seven cases of nonresectable gastric carcinoma with lymph node metastasis were treated with combination chemotherapy [CDDP 75 mg/m2 i.v. day 1 (A method: Ccr > or = 50 ml/min) or 20 mg/m2 i.v. day 1, 2, 4, 5 (B method: Ccr < 50 ml/min), MMC 10 mg/m2 i.v. day 1, etoposide 50 mg/body i.v. day 3, 4, 5, 5'-DFUR 2,100 mg/body po 4 day/week] every 4 weeks as a neoadjuvant chemotherapy. After treatment, the size of the primary tumor was reduced in four of seven cases. The lymph nodes disappeared in one case and were reduced in size in four cases. Metastatic liver tumors were found in four cases. They disappeared in one case and the size was reduced in one of seven cases. One patient with renal dysfunction was treated with B method. However, renal dysfunction did not become worse. Five patients were operated after chemotherapy. Absolute curative resection was performed in three of them. The total rate of curative resection was 43% (3/7). Four patients were alive for 19 months after operation. The main side effects of this therapy were nausea, anorexia and bone marrow suppression, which, were found in all patients. These results suggest that this combination chemotherapy is as effective as neoadjuvant chemotherapy for advanced gastric carcinoma.

Aged↗
PubMed2006

[Neoadjuvant Chemotherapy in breast cancer].

Neoadjuvant chemotherapy for breast cancer was originally used in locally advanced inoperable disease in order to achieve surgical resection. It was then extended to operable breast cancer with a view to downstaging tumors to facilitate breast-conserving surgery. Long-term results from randomized studies have shown no difference in disease-free or overall survival between neoadjuvant and adjuvant chemotherapy. The main benefit of neoadjuvant chemotherapy is its ability to downstage large tumors with a view to treatment by breast-conserving surgery. Since pathological complete response is thought to be main factor to achieve long-term survival, development of new agent or novel combination treatment is needed.

Antineoplastic Combined Chemotherapy Protocols↗