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PubMed2006

Pre-treatment haemoglobin levels and the prediction of response to neoadjuvant chemotherapy in breast cancer.

AIMS: A low pre-treatment haemoglobin level has been shown to negatively influence outcome in the treatment of tumours of the cervix, bladder and head and neck by radiotherapy. The purpose of this study was to assess the influence of baseline haemoglobin levels on the response to neoadjuvant chemotherapy for breast cancer. MATERIALS AND METHODS: One hundred and thirty-nine women receiving neoadjuvant chemotherapy for operable breast tumours (T2-4, N0-1, M0) were accessed from our prospective database. Women were treated between March 1999 and June 2004. The median age was 47 years (range 25-70). Most women were treated with 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy (122/139 patients). Baseline haemoglobin levels were compared for clinical responders (partial or complete) and non-responders (stable or progressive disease) using Student's t test and logistic regression. The analysis was adjusted for nodal status, tumour size, tumour grade and menopausal status. RESULTS: The overall response rate was 84.9% (118/139), with a complete clinical response in 24.5% (34/139). Mean haemoglobin levels were 13.3 g/dl in responders and 13.4 g/dl in non-responders (range 7.9-15.8). The distributions of haemoglobin levels were not significantly different when comparing either responders with non-responders or 'good' responders with 'poor' responders (P = 0.70 and P = 0.32, respectively). If haemoglobin is treated as a binary variable using 12.0 g/dl as the threshold, there is a non-significant trend towards a reduction in the probability of achieving a good response if baseline haemoglobin is below 12.0 g/dl (odds ratio = 0.26, confidence interval = 0.06-1.21; P = 0.086). The rate of complete pathological response was 4.3% (6/139). The mean haemoglobin level in these patients was 14.2 g/dl (range = 12.8-15.7), but the small numbers precluded further analysis. CONCLUSIONS: There is no evidence for an influence of pre-treatment haemoglobin levels on the clinical response to neoadjuvant chemotherapy in breast cancer. It is unlikely that correction of anaemia above that which is warranted clinically will improve outcomes.

Adult↗
PubMed2004

A phase I/II trial of induction chemotherapy with carboplatin and gemcitabine followed by concurrent vinorelbine and paclitaxel with chest radiation in patients with stage III non-small cell lung cancer.

PURPOSE: We designed a phase I/II trial in order to evaluate the efficacy and tolerability of induction carboplatin and gemcitabine and the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of subsequent chemoradiotherapy with weekly vinorelbine and paclitaxel in patients with stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients had pathologically confirmed N2-N3 stage NSCLC, adequate end-organ function, and ECOG performance status 0-2. Carboplatin was administered at an AUC of 5 on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8, every 21 days, for two cycles, followed by weekly vinorelbine 10-15 mg/m2 and paclitaxel 50 mg/m2 and conventional chest radiotherapy up to 66 Gy. Patients with resectable disease underwent thoracotomy after 40-45 Gy. RESULTS: Thirty-nine eligible patients were enrolled; 17 had stage IIIB NSCLC. Grade 3 esophagitis developed in 4/5 patients on the second dose level of chemoradiotherapy (i.e. vinorelbine 15 mg/m2) and was considered dose-limiting. Of 34 patients treated at the maximum tolerated dose (i.e. vinorelbine 10 mg/m2), 2 patients (6%) had pneumonitis >grade 2 and 3 (9%), esophagitis >grade 2. Induction chemotherapy was well tolerated with only one patient developing >grade 2 non-hematologic toxicity (nausea). Forty-one percent of patients had an objective response after induction chemotherapy and 51% after chemoradiotherapy. Nineteen patients, 16 of whom had stage IIIA, underwent surgical resection. The pathologic complete response rate was 16% (42% in the mediastinal lymph nodes). With a median follow-up of 31 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 23 and 34%, respectively, and the median OS was 25 months. CONCLUSIONS: We identified a well-tolerated and active chemoradiotherapy regimen. Survival results are promising and the addition of a biologic agent to this regimen is of interest.

Adult↗
PubMed1998

Primary chemotherapy in locally advanced breast cancer (LABC): effects on tumour proliferative activity, bcl-2 expression and the relationship between tumour regression and biological markers.

The rate of tumour cell proliferation evaluated by the [3H]-thymidine labelling index ([3H]-dT-LI) is known to be an independent prognostic factor in patients with operable breast cancer and significantly predicts the response to chemotherapy in patients with advanced disease. In locally advanced breast cancer (LABG), we examined whether chemotherapy induced modifications in [3H]-dt-LI, and bcl-2 expression and their relationship with tumour regression and prognosis. 70 LABC patients received three courses of primary chemotherapy (FEC: 5-fluorouracil 600 mg/m2, epidoxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2, followed by surgery and subsequent adjuvant chemotherapy consisting of three courses of FEC alternated with three courses of CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, 5-fluorouracil 600 mg/m2). Tumour biological markers were evaluated on diagnostic biopsy, before primary chemotherapy and at surgery. Tumour cell proliferation was determined by [3H]-dT-LI, whilst bcl-2 expression was examined by immunohistochemical staining. The overall response rate to primary FEC was 74.3% (95% confidence interval 57.6-83.2%). The response rate correlated with high [3H]-dT-LI: 88% (29/33) of patients with high [3H]-dT-LI achieved an objective response compared with 62% (23/37) of patients with low [3H]-dT-LI (P = 0.014). The 3 patients achieving a pathological complete response after induction treatment had high proliferative tumours. The highest 2-year relapse free survival (66.6%) was observed in patients with low [3H]-dT-LI after primary chemotherapy. The median bcl-2 expression values before and after primary chemotherapy were 0% (range 0-80) and 30% (range 0-90), respectively (P = 0.03). Our data indicate that primary chemotherapy can modulate tumour cell kinetics and apoptosis-related genes. Pretreatment proliferative activity correlated with tumour response, whilst post-treatment [3H]-dT-LI correlated with relapse free survival.

Adult↗
PubMed2005

Clinical examination following preoperative chemoradiation for rectal cancer is not a reliable surrogate end point.

PURPOSE: Clinical assessment of rectal cancer response to preoperative combined-modality therapy (CMT) using digital rectal examination (DRE) has been proposed as a means of assessing efficacy of therapy. However, because the accuracy of this approach has not been established, we conducted a prospective analysis to determine the operating surgeon's ability to assess response using DRE. PATIENTS AND METHODS: Ninety-four prospectively accrued patients with locally advanced rectal cancer (T3/4 or N1) were evaluated with DRE and sigmoidoscopy in order to determine the following tumor characteristics: size, location, mobility, morphology, and circumference. Following preoperative CMT (50.40 Gy with fluorouracil-based chemotherapy) and under general anesthesia, the same surgeon estimated tumor response based on changes in these tumor characteristics, assessed via DRE. Percent pathologic tumor response was determined prospectively by a single pathologist using whole mount sections of the resected cancer. RESULTS: Clinical assessment using DRE underestimated pathologic response in 73 cases (78%). In addition, DRE was able to identify only 3 of 14 cases (21%) with a pathologic complete response. There were no clinical overestimates of response. None of the clinicopathologic tumor characteristics examined had a significant impact on DRE estimation of response. CONCLUSION: Clinical examination underestimates the extent of rectal cancer response to preoperative CMT. Given the inaccuracy of DRE following preoperative CMT, it should not be used as a sole means of assessing efficacy of therapy nor for selecting patients following CMT for local surgical therapies.

Adult↗
PubMed2006

Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response.

PURPOSE: Preoperative therapy for localized gastric cancer has considerable appeal. We hypothesized that, in a cooperative group setting, preoperative chemoradiotherapy would induce a 20% pathologic complete response (pathCR) rate. Combined-modality therapy quality, survival, and safety were secondary end points. PATIENTS AND METHODS: Patients with localized gastric adenocarcinoma were eligible. A negative laparoscopic evaluation was required. Patients received two cycles of induction fluorouracil, leucovorin, and cisplatin followed by concurrent radiation and chemotherapy (infusional fluorouracil and weekly paclitaxel). Resection was attempted 5 to 6 weeks after chemoradiotherapy was completed. Quality of therapy was assessed with other end points. RESULTS: Twenty institutions participated. Forty-nine patients were entered and 43 were assessable (12% stage IB; 37% stage II; and 52% stage III). The pathCR and R0 resection rates were 26% and 77%, respectively. At 1 year, more patients with pathCR (82%) are living than those with less than pathCR (69%). Grade 4 toxicity occurred in 21% of patients. Chemotherapy, radiotherapy, and surgery per protocol (including acceptable variations) occurred in 98%, 44%, and 63% of patients, respectively. A D2 dissection was performed in 50% of patients. Of 18 major radiotherapy variations, 17 were due to the lack of inclusion of the L3-4 vertebral interphase as prespecified. CONCLUSION: For localized gastric cancer, preoperative chemoradiotherapy strategy achieved a pathCR rate of more than 20% in a cooperative group setting. The quality of surgery improved (50% with D2 dissection) possibly because surgery was part of this trial. With some refinements, this preoperative chemoradiotherapy strategy is poised for a randomized comparison with postoperative adjuvant chemoradiotherapy in patients with gastric cancer.

Adenocarcinoma↗
PubMed2003

Cell-cycle regulators and the Ki-67 labeling index can predict the response to chemoradiotherapy and the survival of patients with locally advanced squamous cell carcinoma of the esophagus.

BACKGROUND: We investigated whether aberrant p53 and p16 expression, the Ki-67 labeling index (LI), and int-2/cyclin D1 gene amplification predict the response to chemoradiotherapy (CRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: p53 and p16 expression status, the Ki-67 LI, and int-2/cyclin D1 amplification were assessed by immunohistochemical staining and slot blot analysis in pretreatment endoscopic biopsy specimens of 41 patients with T4 or M1 Lym (distant lymph node metastasis) ESCC. All patients received a course of chemotherapy (5-fluorouracil and cisplatin) with radiotherapy. RESULTS: The CRT therapeutic response rate was 71%, and resection after CRT was successful in 15 of the cases in which the CRT effect was significant. The cumulative survival rate after CRT in the p53-negative patients was significantly higher than in the p53-positive patients (P =.037). The mean Ki-67 LI in the CRT response cases was significantly higher than in the CRT no-response cases (P =.023). Multivariate regression analysis revealed high Ki-67 LI to be an independent variable linked to a pathologic complete response to CRT (P =.033). The cumulative survival rate after CRT in the group that was p53-negative and int-2/cyclin D1 amplification-positive was significantly higher than in the other groups (P =.008). CONCLUSIONS: Evaluating predictive factors in pretreatment endoscopic biopsy specimens may allow selection of more suitable multimodal treatment for ESCC patients and improve their quality of life.

Adenocarcinoma↗
PubMed1991

Measurement of the ovarian cancer-associated antigen CA 125 in monitoring tumor burden and response to chemotherapy.

CA 125 serum levels were measured in 74 patients with ovarian carcinoma. Among 31 patients undergoing a second look laparotomy (SL) after chemotherapy pathologic complete response (PCR) was observed in 14 patients, residual disease (RD) less than 2 cm in 7 patients and RD greater than 2 cm in 10 patients. The disease status was compared to the CA 125 serum levels measured just before SL. Thirteen of the 14 patients with PCR had serum CA 125 values less than 35 U/ml (specificity: 93%). On the other hand, only 10 of the 17 patients with RD showed serum levels greater than 35 U/ml (sensitivity: 59%). Moreover, in the 43 patients receiving chemotherapy, CA 125 levels correlated with the course of the disease in 36 (84%). With regard to early detection of recurrence, in 9/14 patients with PCR, whose CA 125 levels were monitored monthly, by 1 to 7 months an increase of the tumor marker preceded clinical evidence of relapse in 9/9 relapses (100%). In conclusion, CA 125 assay can be helpful in the management of ovarian cancer patients, in monitoring the response to chemotherapy, in the early detection of tumor recurrence, and in predicting the SL findings, although the low sensitivity could be a major drawback in patients with RD before SL.

Adult↗
PubMed1999

Chemoradiotherapy for advanced inoperable head and neck cancer: A phase II study.

The beneficial effects of chemotherapy in patients with advanced head and neck cancer remain controversial in terms of survival, but have shown some promise in improving locoregional control and quality of life. In an effort to improve locoregional control and survival, a prospective phase II study was initiated using paclitaxel and carboplatin with concurrent conventional fractionated external-beam radiotherapy. Paclitaxel and carboplatin have both shown excellent radiosensitization through two discrete mechanisms, cell blockage in G2/M phase and inhibition of DNA repair, respectively. Patients were stratified as either operable or inoperable. This report pertains to the inoperable patient group, who received eight cycles of weekly paclitaxel (60 mg/m2), carboplatin (area under the concentration-time curve of 1) with conventional radiotherapy (72 Gy). Chemoradiotherapy was followed by neck dissection for those patients who presented with clinically palpable lymph nodes. Thirty-three patients were enrolled in this group (23 men and 10 women with a median age of 56 years). Eleven patients (33%) had stage III disease; 22 (67%), stage IV disease. The median follow-up period was 14 months. Clinical complete response occurred in 20 patients (60%) and partial response occurred in 10 (30%), for an overall response rate of 90%. Following completion of therapy, 18 patients have undergone biopsy at the primary tumor site and 17 were negative. Eight of the 16 patients with clinically palpable neck nodes at presentation underwent neck dissection; five (63%) had negative nodes. Mucositis was the most common toxicity. Grade 3 or 4 mucositis occurred in 30 of the 33 (90%) patients. Other grade 3 or 4 toxicities included skin (22%), candidiasis (19%), neutropenia (9%), and dehydration (6%). One patient with laryngeal carcinoma who had pathologic complete response developed cartilage necrosis and is undergoing hyperbaric oxygen therapy. Survival data are early but encouraging. Concurrent paclitaxel, carboplatin, and external-beam radiotherapy yielded excellent clinical and pathologic responses. Mucositis remains the most common and significant morbidity. The study will continue for necessary accrual.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Randomized phase 2 evaluation of preoperative radiation therapy and preoperative chemotherapy with mitomycin, vinblastine, and cisplatin in patients with technically unresectable stage IIIA and IIIB non-small cell cancer of the lung. LCSG 881.

Between June 1988 and January 1980, 67 patients with pathologic stage III non-small cell lung cancer were randomized to receive either preoperative mitomycin, vinblastine, and cisplatin (MVP) chemotherapy (cisplatin 120 mg/m2, and mitomycin, 8 mg/m2 day 1 + 29, and vinblastine, 4.5 mg/m2 on day 1, 15, 22, and 29 and 2.0 mg/m2 day 8), or preoperative radiotherapy (44 Gy in 22 fractions to the primary tumor and mediastinum). The purpose of this study was to identify a treatment approach that showed sufficient effectiveness and acceptable toxicity to warrant testing by prospective randomized trial against "standard" nonsurgical treatment. All patients had surgical staging of the mediastinum and had either unresectable N2 disease or T4 disease with proximal extension of disease along the pulmonary artery. Response to preoperative therapy was evaluated 8 weeks after beginning treatment and patients with complete or partial radiographic response were to undergo surgical exploration and resection if possible. Fifty-seven patients were eligible and evaluable for response. Of the 67 total patients, 3 were unavailable for follow-up, 4 were ineligible, 1 was canceled, and 2 refused all treatment after having been randomized. Of the eligible and evaluable patients, 49 had stage IIIA and 8 had stage IIIB disease. Randomization was to MVP in 26 cases and to radiotherapy (XRT) in 31. Radiographic response to treatment was virtually identical for the two approaches, with 29 of the 57 evaluable patients achieving objective responses. In patients achieving radiographic response, 24 underwent surgical exploration and 20 underwent resection, of which 18 were complete. The mediastinum was free of tumor in seven patients but only two pathologic complete responses were seen (one each to XRT and MVP). In addition, ten nonresponders underwent surgery; seven underwent resection. Median survival for the entire group is 12 months, with a 27% actuarial survival at 4 years. Two patients died of treatment toxicity during preoperative therapy. Overall toxicity included 2 preoperative toxic deaths and 6 postoperative deaths in 34 patients who underwent surgical exploration (3 each with XRT and MVP) due to adult respiratory distress syndrome (3), myocardial infarction (1), pulmonary edema (1), and esophageal fistula (1), for an overall death rate 8 of 57 (14%) and a perioperative death rate in surgically explored patients of 6/34 (18%). These preoperative regimens, in the population studied herein, were of modest efficacy and substantial toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Intraperitoneal versus intravenous cisplatin in combination with intravenous cyclophosphamide and epidoxorubicin in optimally cytoreduced advanced epithelial ovarian cancer: a randomized trial of the Gruppo Oncologico Nord-Ovest.

Intraperitoneal chemotherapy has a strong biological and pharmacological rationale in the treatment of ovarian cancer. From 1989 to 1996 the present study included 113 patients with FIGO stage II-IV ovarian cancer with residual disease less than 2 cm who were randomly allocated to receive 50 mg/m(2) intraperitoneal cisplatin (CDDP) plus 60 mg/m(2) intravenous epidoxorubicin (EPIDOX) and 600 mg/m(2) intravenous cyclophosphamide (CTX) (ipPEC arm) or 50 mg/m(2) intravenous CDDP plus 60 mg/m(2) intravenous EPIDOX and 600 mg/m(2) intravenous CTX (ivPEC arm). Chemotherapy was repeated every 4 weeks for six cycles. Treatment protocol was changed in 22 patients, 2 from the iv arm (who received single-agent carboplatin) and 20 from the ip arm (who were crossed to systemic chemotherapy, ivPEC, or single-agent carboplatin). At the end of chemotherapy, a second-look was performed in 33 of the 54 patients from the ip arm and in 34 of the 57 patients from the systemic arm. The pathologic complete response rate was 41% of all entered patients and 69% of patients submitted to second-look. No significant difference in pathologic response rate as well as in hematologic and nonhematologic toxicities was seen between the two arms. Up to September 1998, 72 patients showed a disease recurrence (33 treated with ipPEC and 39 treated with ivPEC), 55 died (22 ipPEC and 30 ivPEC), and 10 were lost to follow-up (6 ipPEC and 4 ivPEC). Median progression-free survival was 42 and 25 months for ipPEC and ivPEC, respectively (p = 0.13). Median overall survival was 67 and 51 months for ipPEC and ivPEC, respectively (p = 0.14). In conclusion, besides confirming that intraperitoneal chemotherapy is feasible with acceptable toxicity but with poor compliance in community hospitals, this trial showed that intraperitoneal CDDP compared with intravenous CDDP in combination with EPIDOX and CTX obtained a slight (not significant) improvement in progression-free survival and overall survival of optimally cytoreduced advanced ovarian cancer patients.

Adult↗
PubMed2005

Preoperative second-line chemotherapy induces objective responses in primary breast cancer.

PURPOSE: Preoperative chemotherapy in patients with primary breast cancer results in high response rates, allowing breast-conserving surgery in patients primarily not suitable for this procedure. Tumors of patients with histologically proven breast cancer that fail to respond to preoperative chemotherapy are thought to be chemotherapy resistant. We questioned this hypothesis and treated 13 patients who did not respond to preoperative anthracycline-containing first-line treatment. PATIENTS AND METHODS: Eight patients received a combination therapy consisting of epidoxorubicin and docetaxel as neoadjuvant first-line treatment and were treated with CMF as preoperative second-line chemotherapy. The other five patients did not respond to first-line FEC and were given paclitaxel or docetaxel as second-line treatment. RESULTS: A major response to treatment was observed in 10 of 13 patients (77%) during preoperative second-line therapy: one patient (8%) achieved pathological complete response (pCR) and nine patients (69%) partial response (PR). Three patients (23%) had stable disease (SD), and no patient had progressive disease (PD). Eight patients (62%) could undergo breast-conserving surgery. CONCLUSIONS: We conclude that it is possible to achieve objective responses including pCR with potentially non-cross-resistant neoadjuvant second-line therapy, leading to breast-conserving surgery in a high proportion of patients. Thus, preoperative second-line chemotherapy appears to be justified when breast conservation is an important treatment goal and may have potential in improved tailoring of neoadjuvant treatments.

Adult↗
PubMed2004

Necessity for adjuvant neck dissection in setting of concurrent chemoradiation for advanced head-and-neck cancer.

PURPOSE: Neck dissection has traditionally played an important role in the treatment of patients with squamous cell carcinoma of the head and neck who present with regionally advanced neck disease (N2-N3). Radiotherapy and concurrent chemotherapy improves overall survival in advanced head-and-neck cancer compared with radiotherapy alone. The necessity for postchemoradiation neck dissection is controversial. The intent of this report was to define the value of neck dissection in this patient population better. METHODS AND MATERIALS: Patients with locally advanced squamous carcinoma of the head and neck who also presented with nodal disease and underwent hyperfractionated radiotherapy and concurrent cisplatin/5-fluorouracil chemotherapy constituted the study population. Adjuvant modified neck dissection (MND) was planned 6 to 8 weeks after completion of chemoradiation in those patients who had a biopsy-proven pathologically complete response at the primary tumor site, irrespective of the clinical/radiographic neck response. A cohort of patients underwent electrode assessment of tumor oxygenation. Pathologic findings from the MND were used to compute the negative and positive predictive values and overall accuracy of the clinical/radiographic response (cCR). Regional control, failure-free survival, and survival were compared according to whether patients actually underwent MND. RESULTS: A total of 154 patients received concurrent chemoradiation. Of these, 108 presented with nodal disease: N1, n = 30; and N2-N3, n = 78. MND was performed in 65 (60%) of 108 patients, including 13 (43%) of 30 with Stage N1 and 52 (66%) of 78 with Stage N2-N3. For N1 patients, the negative predictive value of a cCR, positive predictive value of less than a cCR, and the overall accuracy for clinical response was 92%, 100%, and 92%, respectively. For N2-N3 patients, the corresponding values were 74%, 44%, and 60%. Patients with poorly oxygenated tumors were more likely to have residual disease at MND. The median follow-up was 4 years. The 4-year disease-free survival rate was 70% for N1 patients, irrespective of the clinical response or whether MND was performed. The 4-year disease-free survival rate was 75% for N2-N3 patients who had a cCR and underwent MND vs. 53% for patients who had a cCR but did not undergo MND (p = 0.08). The 4-year overall survival rate was 77% vs. 50% for these two groups of patients (p = 0.04). CONCLUSION: The clinical and pathologic responses in the neck correlated poorly with one another for patients with N2-N3 neck disease undergoing concurrent chemoradiation for advanced head-and-neck cancer. MND still appears to confer a disease-free survival and overall survival advantage with acceptably low morbidity. Tumor oxygenation assessment may be useful in selecting patients who are especially prone to have residual disease. Better tools need to be developed to determine prospectively whether this procedure is required for individual patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Clinical and biomarker endpoint analysis in neoadjuvant endocrine therapy trials.

Neoadjuvant endocrine therapy trials for breast cancer are now a widely accepted investigational approach for oncology cooperative group and pharmaceutical company research programs. However, there remains considerable uncertainty regarding the most suitable endpoints for these studies, in part, because short-term clinical, radiological or biomarker responses have not been fully validated as surrogate endpoints that closely relate to long-term breast cancer outcome. This shortcoming must be addressed before neoadjuvant endocrine treatment can be used as a triage strategy designed to identify patients with endocrine therapy "curable" disease. In this summary, information from published studies is used as a basis to critique clinical trial designs and to suggest experimental endpoints for future validation studies. Three aspects of neoadjuvant endocrine therapy designs are considered: the determination of response; the assessment of surgical outcomes; and biomarker endpoint analysis. Data from the letrozole 024 (LET 024) trial that compared letrozole and tamoxifen is used to illustrate a combined endpoint analysis that integrates both clinical and biomarker information. In addition, the concept of a "cell cycle response" is explored as a simple post-treatment endpoint based on Ki67 analysis that might have properties similar to the pathological complete response endpoint used in neoadjuvant chemotherapy trials.

Antineoplastic Agents, Hormonal↗
PubMed2001

A phase II study of gemcitabine and cisplatin combination as induction chemotherapy for untreated locally advanced cervical carcinoma.

BACKGROUND: Cisplatin-based chemoradiation for locally advanced cervical carcinoma is now the standard of care for most patients with cervical carcinoma. However, induction chemotherapy followed by surgery, particularly with newer agents or combinations remains to be explored. This study was undertaken to evaluate the antitumor activity and toxicity of gemcitabine in combination with cisplatin for untreated locally advanced cervical carcinoma. PATIENTS AND METHODS: Open-label, single center, phase II, non-randomized study of neoadjuvant gemcitabine plus cisplatin. Forty-one patients with histologic diagnosis of cervical carcinoma, with no previous treatment and staged as IB2 to IIIB, were treated with three 21-day courses of cisplatin 100 mg/m2 day I and gemcitabine 1000 mg/m2 days 1 and 8, followed by locoregional treatment with either surgery or concomitant chemoradiation. Response and toxicity were evaluated before each course and at the end of chemotherapy. RESULTS: All patients were evaluated for toxicity and 40 for response. The overall objective response rate was 95% (95% confidence interval (CI): 88%-100%) being complete in 3 patients (7.5%) and partial in 35 (87.5%). A complete pathological response was found in 6 (26%) of the 23 patients that underwent surgery. Granulocytopenia grades 3-4 occurred in 13.8% and 3.4% of the courses, respectively, whereas non-hematological toxicity was mild. CONCLUSIONS: Induction chemotherapy with the combination of gemcitabine and cisplatin is highly active for untreated cervical cancer patients and has an acceptable toxicity profile.

Adenocarcinoma↗
PubMed1996

Concurrent radiation therapy and chemotherapy followed by esophagectomy for localized esophageal carcinoma.

PURPOSE: A prospective study was performed to determine the outcome of patients with esophageal cancer who received preoperative radiation therapy and chemotherapy followed by esophagectomy, and to determine the role of preresection esophagogastroduodenoscopy (EGD) in predicting the patients in whom surgery could possibly be omitted, and the impact of surgery on survival. MATERIALS AND METHODS: Thirty-five patients with localized carcinoma of the esophagus received concurrent external-beam radiotherapy and chemotherapy followed by esophagectomy. Patients received 45 Gy in 25 fractions. Chemotherapy consisted of continuous infusion fluorouracil (5-FU; 1,000 mg/m2/d) on days 1 through 4 and 29 through 32 and cisplatin (100 mg/m2) on day 1. Patients underwent an Ivor-Lewis esophagectomy 18 to 33 days after completion of radiotherapy. RESULTS: Eighty percent of the patients had squamous cell carcinoma and 20% had adenocarcinoma. In addition, 51% had a pathologic complete response (CR). Twenty-two of the 35 underwent a preresection EGD before resection. Seventeen of the 22 (77%) had negative pathology from the preresection EGD, but seven of the 17 (41%) had residual tumor at surgery. The median survival and disease-free survival rates for all patients were 25.8 months and 32.8 months, respectively. Eighteen patients (51%) had no tumor at resection. The median survival for these patients was 36.8 months; the median disease-free survival time has not been reached. The median survival and disease-free survival rate for the patients with residual tumor in the surgical specimen were 12.9 months and 10.8 months, respectively. CONCLUSION: Preresection EGD is not reliable for determining the presence of residual disease or the patients in whom surgery could be omitted. Twenty-five percent of the patients with residual tumor in the resected surgical specimen were long-term survivors; this suggests a benefit from esophagectomy after concurrent radiotherapy and chemotherapy.

Adenocarcinoma↗
PubMed2003

Induction chemotherapy for breast carcinoma: predictive markers and relation with outcome.

Induction chemotherapy provides an excellent model for evaluation of potential predictive factors. We studied expression of SBR grade, estrogen (ER) and progesterone (PR) receptors, HER2, Ki67 and P53 on core biopsies before and after chemotherapy in a series of 115 patients, who received anthracycline-based induction chemotherapy for primary breast cancer. HER2 overexpression independently predicted response to neoadjuvant anthracycline-based chemotherapy. Patients with HER2-positive status are 4.54 times more likely to have a pathological complete response than those with negative status (p<0.005). HER2, ER and PR status were stable during treatment. P53 and Ki67 significantly increased after treatment (p<0.005 and p<0.0005). SBR grade, proliferation markers, ER evaluated before and after treatment predicted disease-free survival (DFS) in univariate analysis.

Aneuploidy↗
PubMed2004

Preoperative induction of CPT-11 and cisplatin chemotherapy followed by chemoradiotherapy in patients with locoregional carcinoma of the esophagus or gastroesophageal junction.

BACKGROUND: Patients with localized esophageal carcinoma often develop locoregional and distant disease recurrence. The current study investigated the outcome of a new chemotherapy combination as induction therapy before chemoradiotherapy. METHODS: Forty-three patients with resectable carcinoma of the esophagus or gastroesophageal junction were enrolled. Most of the tumors were endoscopic ultrasonography (EUS) (EUS)T3 (84%) and (EUS)N1 (63%). The patients received < or = 2 6-week cycles of CPT-11 and cisplatin followed by chemoradiotherapy (45 grays with 5-fluorouracil and paclitaxel). Five to six weeks after chemoradiotherapy, the patients underwent staging and surgery. The feasibility, curative resection rates, overall and disease-free survival rates, rate of significant pathologic response, and patterns of disease recurrence were assessed. RESULTS: Of the 43 patients, 39 (91%) underwent an R0 resection. Two patients (5%) died after surgery. A pathologic complete response (pathCR) was observed in 11 (28%) of the 39 patients (or 26% of the 43 patients). In addition, 16 patients (41% of 39 patients or 37% of 43 patients) had < 10% viable tumor in the surgical specimen (pathPR). A comparison of endoscopic ultrasonograpy T and N classifications with surgical T and N classifications demonstrated significant down-staging (P < 0.01). The median survival period of all 43 patients was 22.1 months. Patients who had achieved a pathCR or pathPR had a longer median survival (25.6 months) than those who achieved less than a pathPR (18.5 months; P = 0.52). None of the clinical parameters examined were found to correlate with survival or pathologic response. CONCLUSIONS: CPT-11-based induction chemotherapy resulted in substantial pathCR and pathPR rates, both of which lead to a favorable survival outcome. The three-step strategy needs to be developed further, with the investigation of targeted therapies with chemotherapy and radiotherapy.

Adenocarcinoma↗
PubMed1993

Induction chemotherapy for locally advanced non-small cell lung cancer.

The poor survival of patients with stage III non-small cell lung cancer has led to a reevaluation of the role of systemic chemotherapy administered before operation. The results of 15 phase-II pilot trials of induction chemotherapy (5 with chemotherapy alone; 4 with chemotherapy and radiotherapy; and 6 with chemotherapy and concurrent radiotherapy) are reviewed in this article, and recommendations for future randomized studies are made. For most trials, only patients in stage IIIa were eligible, but five trials included both IIIa and IIIb patients. The studies employed a variety of chemotherapy and radiotherapy induction protocols, but no superiority could be demonstrated for the administration of chemotherapy and radiotherapy over chemotherapy alone. Response was observed in more than 50% of patients overall, although the complete clinical remission rate was always less than 15%, and the pathologic complete response rate was usually less than 10%. After induction therapy, approximately 70% of patients were eligible for a thoracotomy, and complete resection was possible in 60% of patients. The median survival ranged from 8 to 32 months, with a median of approximately 1 1/2 years. Two-year to 3-year survival ranged from 25% to 30%. The studies reviewed showed that induction therapy followed by surgical resection is feasible and is not associated with unacceptable toxicity. The apparent survival benefit conferred by such combined modality treatment may be due to patient selection, and until randomized trials are undertaken, induction therapy and surgical intervention for locally advanced non-small lung cancer must be viewed as experimental.

Antineoplastic Combined Chemotherapy Protocols↗