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At least 199 records · Page 11Linked to original sources
PubMed2002

Long-term results of combined-modality therapy in resectable non-small-cell lung cancer.

PURPOSE: Assessment of long-term results of combined-modality therapy for resectable non-small-cell lung cancer is hampered by insufficient follow-up and small patient numbers. To evaluate this, we reviewed our collective experience. PATIENTS AND METHODS: This study was a retrospective chart review recording demographics, tumor stage, treatment, and outcome of consecutive patients undergoing surgery. Survival was analyzed by Kaplan-Meier, and prognostic factors were analyzed by log-rank and Cox regression. RESULTS: From January 1993 to December 1999, 470 patients were treated, with follow-up in 446: 27 stage I, 55 stage II, 316 stage III, 43 stage IV (solitary M1), and five uncertain. Chemotherapy was mitomycin/vinblastine/cisplatin (174 patients [39.0%]), carboplatin/paclitaxel (148 [33.2%]), and other combination (124 [27.8%]); 75 patients (16.8%) received induction radiation. Resection was complete in 77.4%, incomplete in 8.3%, attempted but with gross residual disease afterward in 1.8%, and not performed in 12.6%. Pathologic complete response occurred in 20 patients (4.5%). With median follow-up of 31.0 months for patients still alive, median and 3-year survival for pathologic stages 0, I, II, III, and IV were more than 90 months, 73%; 42 months, 52%; 23 months, 35%; 16 months, 28%; and 16 months, 23% (P <.001). In a multivariate analysis, age, complete resection, pathologic stage, and pneumonectomy, but not induction regimen, significantly influenced survival. CONCLUSION: Although pathologic complete response outside the protocol setting is low, survival of this large patient cohort is comparable to that of patients in published combined-modality trials. Survival is significantly influenced by patient age, complete resection, pathologic stage, and pneumonectomy. These results can help guide standard clinical practice and emphasize the need for novel induction regimens.

Adult↗
PubMed1994

Phase II trial of intraperitoneal carboplatin in ovarian carcinoma patients with macroscopic residual disease at second-look laparotomy. A multicentre study of the French Fédération Nationale des Centres de Lutte Contre le Cancer.

BACKGROUND: Because of its antitumour activity and its pharmacological advantage when administered by the intraperitoneal route, carboplatin was studied in a phase II multicentric trial. The aim of the study was to determine the response rate and the toxicity of carboplatin administered intraperitoneally and to determine if pathological complete response could be attained in women with macroscopic residual ovarian cancer at second-look laparotomy after intravenous cisplatin chemotherapy. PATIENTS AND METHODS: Twenty-nine patients with macroscopical residual disease after intravenous cisplatin-based chemotherapy at second-look laparotomy, were treated at that time with 300 mg/m2 of carboplatin administered in the abdominal cavity every four weeks for six cycles. In instances of negative findings at physical and CT scan examination, laparotomy evaluation was performed and the catheter was removed. The dose of carboplatin was increased or decreased according to hematological toxicity. RESULTS: Efficacy is evaluable in 25 pts: 2 pts had pathological complete responses and 1 pt had microscopic disease (12% response rate of evaluable patients). Toxicity is evaluable for 135 cycles in 29 patients. No grade 4 hematological toxicity was observed, 2 pts had grade 3 leukopenia and 3 pts had grade 3 thrombocytopenia; grade 3 vomiting was observed in 11% of cycles. No peritoneal complication was observed; catheter dysfunction occurred after the first cycle in one patient who refused a surgical procedure to remove the catheter and to pursue treatment. CONCLUSION: Intraperitoneal carboplatin demonstrates efficacy in patients with macroscopical residual disease at second-look laparotomy after first-line cisplatin chemotherapy. The recommended dose for further studies is 300 mg/m2 administered every 4 weeks. A low response rate does not favour a randomised study.

Adult↗
PubMed2001

Concurrent ifosfamide-based chemotherapy and irradiation. Analysis of treatment-related toxicity in 43 patients with sarcoma.

BACKGROUND: The current study was performed to evaluate the toxicity profile of therapeutic doses of ifosfamide (IFX) given concurrently with full-dose external beam radiotherapy (EBRT) in patients with soft tissue and bone sarcomas. METHODS: The medical records of 43 consecutive patients with soft tissue or bone sarcomas who were treated with concurrent IFX and EBRT were reviewed. RESULTS: The median patient age was 20 years. Histologies were rhabdomyosarcoma (n = 16 patients), Ewing sarcoma (n = 10 patients), malignant fibrous histiocytoma (n = 9 patients), and other soft tissue sarcomas (n = 8 patients). Thirty-one patients (72%) had localized disease, and 12 patients (28%) had synchronous local and distant disease. Treatment consisted of EBRT (median dose, 50.4 gray [Gy]) with concomitant IFX (median dose per cycle, 10.2 g/m(2)). All patients with Ewing sarcoma or rhabdomyosarcoma received additional concurrent chemotherapy. Twenty-six patients (60%) received two or more cycles of IFX, and 17 patients (40%) were treated with one cycle of IFX and EBRT. The incidences of World Health Organization Grade 3 and Grade 4 toxicities were 29% (21 of 73 cycles) and 22% (16 of 73 cycles), respectively. Grade 4 systemic toxicities included leukopenia (n = 14 patients), neurotoxicity (suicidal ideation; n = 1 patient), and diarrhea (n = 1 patient). Confluent moist desquamation (Grade 3) occurred in nine patients in the treatment field; no patient experienced Grade 4 local toxicity. Among 14 patients who were treated preoperatively, 2 patients (14%) had a pathologic complete response, and 6 patients (43%) had a pathologic near-complete response (> or = 90% necrosis). CONCLUSIONS: Local and systemic toxicities after the administration of therapeutic doses of IFX with concomitant EBRT appear comparable to those observed with either treatment alone. These results support the design of prospective studies evaluating concurrent ifosfamide and radiation therapy for patients with sarcomas.

Adult↗
PubMed2003

In vivo detection of resistance to anthracycline based neoadjuvant chemotherapy in locally advanced and inflammatory breast cancer with technetium-99m sestamibi scintimammography.

Neoadjuvant chemotherapy (NACT) is the treatment of choice in patients (pts) with locally advanced (LABC) and inflammatory breast cancer (IBC). To evaluate the role of Tc-99m sestamibi imaging in the prediction of response to NACT and in the in vivo functional detection of intrinsic or acquired chemoresistance, 24 female pts with LABC (n=21) or IBC (n=3) were prospectively studied. Tc-99m scintimammography was performed 1-3 days before treatment (first) and 2-5 days after the completion (second) of NACT (epirubicin and cyclophosphamide for LABC and doxorubicin and vinorelbine for IBC). Three planar images (2 lateral prone and one anterior supine, 10 min/each) were obtained 10 min postinjection and a lateral prone image (10 min) of the affected breast (B) was obtained at 4 h. To calculate the tumor to normal B ratio (TBR), 2 identical irregular regions of interest (ROIs) were drawn around the tumor (T) and in adjacent ipsilateral normal B on both early (E) and delayed (D) prone lateral images. The TBR was obtained as the ratio of the mean counts per pixels in the 2 ROIs. Then Tc-99m sestamibi retention index (RI) in the T was determined by dividing the D-TBR by the E-TBR. Afterwards, NACT response was assessed pathologically or clinically in inoperable disease. Scintigraphic sensitivity for correct prediction of T presence after NACT was 81% (17/21), whereas specificity for correct prediction of T absence was 100% (3/3). In LABC, 3 patients had a pathological complete response: first RI was high (>0.56) in all 3, while no T uptake was visible on the second scintigraphy. Eighteen patients did not show a pathological complete response: in 5, both first and second RI were low (</=0.56); 9 had high first RI but low second; 4 had high first RI and no T detected on the second scan. In IBC, the only patient with a clinical complete response had both first and second RI high, whereas the 2 non-responsive pts had both first and second RI low. These results indicate that Tc-99m sestamibi scintimammography can predict LABC and IBC response to NACT. The scintigraphy protocol, including 2 studies before and after NACT, is useful for detecting intrinsic and acquired chemoresistant BC in vivo, which is important for planning therapy and predicting prognosis.

Adult↗
PubMed2004

Clinical experience of weekly paclitaxel-based treatment as preoperative chemotherapy for patients with primary breast cancer.

BACKGROUND: Paclitaxel is an effective agent in the treatment of metastatic breast cancer. The aim of this study was to evaluate the safety and efficacy of weekly paclitaxel-based preoperative chemotherapy in patients with large operable breast cancer. METHODS: Patients initially received paclitaxel as a 3-hour infusion at 175 mg/m2. Three weeks after initial administration, two cycles of three weeks of paclitaxel 80 mg/m2 over a 1 hour infusion followed by a one week break were given. Of 22 patients, 9 had stage II (tumor diameter greater than 3 cm), 4 stage III A, 7 stage III B, and 2 stage IV (with ipsilateral supraclavicular lymph node metastasis) cancer, respectively. RESULTS: Excluding stage IV patients, the overall response rate to paclitaxel chemotherapy was 80%. Four of the 20 patients (20%) showed a clinical complete response (cCR). Two of these showed pathologic complete response and the other 2 had only the ductal component remaining. The primary tumor response and axillary lymph node downstaging following preoperative chemotherapy tended to be related in 16 patients with clinically positive nodes. Breast conserving surgery was performed as a result of downstaging in the 9 stage II patients. Grade 3 neutropenia occurred in one patient when 175 mg/m2 of paclitaxel was administered, but no serious side effects developed during the weekly administration of paclitaxel. CONCLUSION: The use of weekly paclitaxel-based preoperative chemotherapy appears to yield a significant anti-tumor effect without inducing serious drug-related adverse effects. Furthermore, the effectiveness of this treatment appears to result in a higher frequency of breast conserving surgery.

Antineoplastic Agents, Phytogenic↗
PubMed2001

P27kip1 expression is associated with tumor response to preoperative chemoradiotherapy in rectal cancer.

BACKGROUND: Our aim was to ascertain whether or not the response to preoperative chemoradiotherapy for rectal cancer is associated with p27kip1 and p53 protein expression. METHODS: Thirty-eight patients (27 male, 11 female) with a mean age of 59 years (age range 33-87) and stage II-III rectal cancer received preoperative chemoradiotherapy (45-50.4 Gy; 5-FU 350 mg/m2/day and leucovorin 10 mg/m2/day). Thirty-one underwent low anterior resection; seven underwent abdominoperineal excision. Endoscopic tumor biopsies, performed before adjuvant therapy, were evaluated for: histologic type, tumor differentiation, mitotic index, and p27kip1 and p53 protein expression which were immunohistochemically determined. p53 expression was graded as: a) absent or present in < or =10% of tumor cells; b) present in 11-25%; c) present in 26-75%; and d) present in >75% of tumor cells. p27kip1 expression was assessed using both light microscopy (percent of stained cells x10 HPF) and cytometry with an image analysis workstation. Tumor response, ascertained with histology, was classified using a scale from 0 (no response) to 6 (complete pathologic response). RESULTS: The mitotic index for the endoscopic biopsies was low in 14 cases, moderate in 17 cases, and high in 7 cases. p53 protein expression was found in 21 (a), 3 (b), 3 (c), and 11 (d) cases. The mean percentage of cells expressing the p27kip1 protein was 34 (range 0-77.14%). A close correlation was found between cytometric and light microscopy findings for p27kip1 (r2 = 0.92, P = .0001). Tumor differentiation was good in 5 cases, poor in 2 cases, and moderate in the remaining 31 cases. While the response to adjuvant therapy was good/complete in 25 (65.78%) cases, it was absent/poor in 13 (34.21%) cases. Univariate analysis associated type of adjuvant therapy (chemoradiotherapy, P = .0428) and p27kip1 protein lower expression (P = .0148) with a poor response to adjuvant treatment. Stepwise linear regression found overexpression of p53 and p27kip1 and young age to be independent variables that were linked to a good response to adjuvant therapy. CONCLUSIONS: Lack of p27kip1 and p53 protein expression in rectal cancer is associated with a poor response to preoperative adjuvant therapy.

Adult↗
PubMed2001

Surgical resection is necessary to maximize tumor control in function-preserving, aggressive chemoradiation protocols for advanced squamous cancer of the head and neck (stage III and IV).

BACKGROUND: The role of surgery in aggressive chemoradiation protocols for advanced head and neck cancer has been questioned because of the quoted high clinical response rates in many series. METHODS: The role of surgical resection was examined in an aggressive neoadjuvant protocol of weekly paclitaxel, carboplatin, and radiation for stage III and IV with completion of radiation to 72 Gy if biopsy at the primary site was negative after administration of 45 Gy. Of 43 patients enrolled, 38 completed the protocol. The clinical response was 100% (including 18 complete and 20 partial responses). RESULTS: The complete pathologic response (negative primary site biopsy at 45 Gy) was 25 of 38 (66%). Of patients who presented with N1 to N3 nodes, neck dissection revealed residual nodal metastases in 22%. Surgical resection of the primary site was required in 13 patients, including 5 with larynx cancer and 2 with base of tongue cancers. Four patients had resection with reconstruction for advanced mandible floor of mouth cancer, and one had resection of nasal-maxillary cancer. Functional resection was performed in 9 of 12 patients. The median progression free and overall survival was 64% and 68%, respectively, at median follow-up of 50 months. Nine patients developed recurrence (three local and six distant). There were no failures in the neck. Salvage surgery was performed in one patient with local and one with distant disease. CONCLUSIONS: Surgical resection is an essential component of aggressive chemoradiation protocols to ensure tumor control at the primary site and in the neck.

Adult↗
PubMed2006

Intensity-modulated radiotherapy for the treatment of vulvar carcinoma: a comparative dosimetric study with early clinical outcome.

OBJECTIVES: To assess early clinical outcome of intensity-modulated radiation therapy (IMRT) in the treatment of vulvar cancer and compare dosimetric parameters with 3D conformal radiotherapy (3D CRT). METHODS: Fifteen patients with vulvar cancer were treated with IMRT. Seven patients were treated with preoperative chemoradiation, and 8 patients were treated with adjuvant postoperative radiation therapy. Median dose was 46 Gy in the preoperative and 50.4 Gy in the postoperative group. RESULTS: The mean volume of small bowel, rectum, and bladder that received doses in excess of 30 Gy with IMRT was reduced when compared with 3D CRT. Treatment was well tolerated, and only 1 patient had acute Grade 3 small-bowel toxicity. Median follow-up was 12 months. In the preoperative group, 5 patients (71%) had clinical complete response and 3 patients (42.8%) had pathologic complete response. In the adjuvant group, 2 patients had recurrences in the treatment field. No patients had late Grade 3 toxicity. The 2-year actuarial disease-specific survival was 100%. CONCLUSIONS: Intensity-modulated RT appears to offer advantages over 3D CRT treatment of vulvar cancer by elimination of dose modulation across overlapping regions and reduction of unnecessary dose to the bladder, rectum, and small bowel. Early results with a small number of patients show promising results, with a low incidence of severe toxicity.

Adult↗
PubMed1999

Phase II study of radiochemotherapy with UFT and low-dose oral leucovorin in patients with unresectable rectal cancer.

PURPOSE: To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration (UFT) plus low-dose leucovorin administered concomitantly with pelvic irradiation in patients with unresectable or recurrent rectal cancer. METHODS AND MATERIALS: Thirty-five patients (22 with primary unresectable tumors and 13 with locally recurrent tumors) were enrolled in the trial. Thirty-five patients were evaluable for toxicity and 32 of these were evaluable for clinical response. Patients received 300 mg/m2/day UFT and 30 mg/day leucovorin on days 8-35 concomitantly with pelvic radiotherapy, to a total dose of 45 Gy. RESULTS: Eight of the 35 (23%) patients developed Grade 3 diarrhea and were treated with radiotherapy alone after this event. Of the 22 patients with unresectable primary tumors, 17 underwent surgery, and resection was feasible in 15 cases (88%). Of the 32 patients evaluable for clinical response, 4 (13%) had a complete clinical response (CR) and 22 (69%) a partial response (PR). A complete pathologic response was observed in 3 cases (18%) and, a PR in 11 cases (65%). CONCLUSION: The response rates achieved with this schedule seem comparable to those obtained with 5-FU and radiotherapy. These results warrant further evaluation of this combination in patients with unresectable or locally advanced tumors.

Adult↗
PubMed2002

Extracellular matrix proteins and chemoradiotherapy: alpha5beta1 integrin as a predictive marker in rectal cancer.

AIMS: To investigate the effects of extracellular matrix (ECM) protein expression on the rates of apoptosis and proliferation in rectal cancers and subsequent response to chemoradiotherapy (CRT). METHODS: The expression of fibronectin, collagen IV, laminin and the fibronectin receptor (FnR, alpha5beta1 integrin) were analysed in 32 pre-treatment rectal cancer biopsies by immunohistochemistry. ECM expression was correlated with tumour mitotic index (MI), apoptotic index (AI) and histopathological response to CRT. RESULTS: 18/32 cancers showed a poor response and 14/32 a good response (5/14 with complete pathological response) to CRT. Moderate to strong staining was seen in 22/32 cancers for fibronectin, 5/32 for collagen IV and 18/32 for laminin. Tumour FnR was related to stromal fibronectin content, and was significantly associated with CRT response; good responders having higher FnR expression compared to poor responders. No association was found between FnR expression and either MI or AI in pre-treatment biopsies, nor between MI or AI and CRT response. CONCLUSIONS: Tumour FnR expression is independent of MI and AI, and may serve as a useful marker for CRT response in rectal cancer.

Apoptosis↗
PubMed2002

Esophageal carcinoma: surgery, radiotherapy, and chemotherapy.

Several new developments in the potentially curative therapy of esophageal cancer have drawn attention over the past year. There is a potential benefit of centralization of esophagectomies in dedicated centers. Early mucosal lesions are increasingly treated by local ablative therapy. Tumors invading the submucosa are preferably treated by surgical resection. There is ongoing controversy about the optimal surgical approach. Positron emission tomography scanning is a promising tool in the preoperative work-up but needs critical evaluation. The question of whether chemoradiation with voice preservation (followed by salvage surgery in case of tumor recurrence) can replace pharyngolaryngectomy in patients with cervical esophageal cancer is still unanswered. A review of eight randomized trials demonstrated that chemoradiation as primary treatment of esophageal cancer provides an absolute reduction of mortality. The addition of new drugs like paclitaxel and irinotecan into induction regimens for the treatment of advanced disease results in higher response rates but also in increased toxicity. Preoperative radiotherapy as single modality treatment does not improve overall survival, whereas the benefit of preoperative chemotherapy and chemoradiation has not been proven unequivocally. Several retrospective studies with a small number of patients suggest that local response parameters like pathologic complete response and downstaging of regional lymph node (N) status are correlated with longer survival.

Journal Article↗
PubMed1992

Therapy of patients with metastatic breast cancer with 5-fluorouracil, leucovorin and carboplatin.

Thirty-four women with metastatic breast cancer were treated at the National Cancer Institute of the National Institutes of Health, with a regimen of leucovorin (L), 500 mg/m2 i.v. over 30 min, followed in 1 h by 5-fluorouracil (5-FU), 375 mg/m2 i.v. bolus on days 1-5, and carboplatin (CBDCA), 50-100 mg/m2 i.v. bolus on days 2-4, every 28 days. All patients had received previous combination chemotherapy with at least one regimen (29 patients with 5-FU-containing regimens). CBDCA, 100 mg/m2 on days 2-4, resulted in grade 4 neutropenia in 10 out of 11 patients associated with sepsis in all 10 patients. CBDCA, 75 mg/m2 (seven patients) and 50 mg/m2 (15 patients), resulted in grade 4 neutropenia in six and eight patients, and neutropenic sepsis in five and two cases, respectively. Grade 4 thrombocytopenia occurred in 10, five and two patients receiving 100, 75 and 50 mg/m2 of CBDCA, respectively. Other toxicities included grade 3/4 mucositis in 18 patients and grade 3/4 diarrhea in 10 patients. Twenty nine patients were evaluable for response, with one pathologic complete response (3%), two partial responses (6%), 18 stable disease (53%) and eight (24%) progressive disease. Sites of response included bone, viscera and soft tissue. The median time from entry on study to progression, for responders, was 15 months. When platinum-DNA adduct formation in peripheral white blood cells was analyzed in 27 patients at 24 h after drug administration, a significant correlation between adduct level and CBDCA cumulative dose was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1997

Weekly cisplatin given for 2 months versus cisplatin plus cyclophosphamide given for 5 months after cytoreductive surgery for advanced ovarian cancer.

PURPOSE: To compare the efficacy of a treatment with cisplatin plus cyclophosphamide given for 5 months and a short treatment with cisplatin alone in advanced ovarian cancer, we conducted a multicenter randomized clinical trial. PATIENTS AND METHODS: Eligibility criteria were as follows: first diagnosis of histologically confirmed invasive epithelial ovarian cancer of International Federation of Gynecology and Obstetric (FIGO) stage III-IV, age younger than 75 years, and Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. Within 28 days of cytoreductive surgery, eligible women were randomly assigned treatment with weekly cisplatin 50 mg/m2 for nine courses or cisplatin 75 mg/m2 plus cyclophosphamide 750 mg/m2 every 21 days for six courses. RESULTS: A total of 607 women were entered onto the study. There was no difference in the response to treatment. Pathologic complete response (CR) was documented in 63 of the weekly cisplatin cases and 70 of the cisplatin plus cyclophosphamide group (chi 1(2) = 1.43; P = .23). The median follow-up time was 3 years. There were 151 and 148 deaths in the weekly cisplatin and cyclophosphamide plus cisplatin arms, respectively. Survival curves were similar in the two groups, with a 3-year percent survival estimate of 44.1 (SE = 3.4) in the weekly cisplatin and 44.6 (SE = 3.4) in the cisplatin plus cyclophosphamide group (log-rank test chi 1(2) = 0.004; P = .96). CONCLUSION: This study found that 2-month monochemotherapy treatment with cisplatin was as effective as 5-month polychemotherapy including cisplatin at a similar doses but different dose-intensity plus cyclophosphamide.

Adult↗
PubMed2003

Phase I trial of escalating-dose irinotecan given weekly with cisplatin and concurrent radiotherapy in locally advanced esophageal cancer.

PURPOSE: To identify the maximum-tolerated dose and dose-limiting toxicity (DLT) of weekly irinotecan combined with cisplatin and radiation in esophageal cancer. PATIENTS AND METHODS: Nineteen patients with clinical stage II to III esophageal squamous cell or adenocarcinoma were treated on this phase I trial. Induction chemotherapy with weekly cisplatin 30 mg/m2 and irinotecan 65 mg/m2 was administered for four treatments during weeks 1 to 5. Radiotherapy was delivered weeks 8 to 13 in 1.8-Gy daily fractions to a dose of 50.4 Gy. Cisplatin 30 mg/m2 and escalating-dose irinotecan (40, 50, 65, and 80 mg/m2) were administered on days 1, 8, 22, and 29 of radiotherapy. DLT was defined as a 2-week delay in radiotherapy for grade 3 to 4 toxicity. RESULTS: Minimal toxicity was observed during chemoradiotherapy, with no grade 3 or 4 esophagitis, diarrhea, or stomatitis. DLT caused by myelosuppression was seen in two of six patients treated at the 80-mg/m2 dose level, thus irinotecan 65 mg/m2 was defined as the recommended phase II dose. Dysphagia improved or resolved after induction chemotherapy in 13 (81%) of 16 patients who reported dysphagia before therapy. Only one patient (5%) required a feeding tube. Six complete responses (32%) were observed, including four pathologic complete responses in 15 patients selected to undergo surgery (27%). CONCLUSION: Cisplatin, irinotecan, and concurrent radiotherapy can be administered on a convenient schedule with relatively minimal toxicity and an acceptable rate of complete response in esophageal cancer. Further phase II evaluation of this regimen is ongoing. A phase III comparison to fluorouracil or taxane-containing chemoradiotherapy should be considered.

Adult↗
PubMed2006

Capecitabine: expanding options for the treatment of patients with early or locally advanced breast cancer.

Capecitabine has proven efficacy in metastatic breast cancer, extending survival in combination with docetaxel and offering a favorable safety profile, including minimal myelosuppression and alopecia, as a single agent. It is therefore logical that capecitabine could build on the improved outcomes achieved with taxanes in early breast cancer. In the neoadjuvant setting, a phase III trial of capecitabine and docetaxel (XT) versus doxorubicin and cyclophosphamide (AC) showed that XT was more effective than AC in terms of clinical response rate and pathologic complete response rate, with a manageable safety profile. Other studies, including a phase III trial of capecitabine, epirubicin, and docetaxel, a phase III trial of capecitabine and vinorelbine, and several phase II studies of different regimens with capecitabine, have confirmed the high activity of neoadjuvant capecitabine, with acceptable safety. In the adjuvant setting, a Finnish phase III study (FinXX) of sequential XT followed by cyclophosphamide, epirubicin, and capecitabine versus docetaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide has shown favorable safety with lower doses of both capecitabine and docetaxel in the XT combination. Efficacy results from that trial are eagerly awaited. A large, ongoing trial program is continuing to explore the potential for capecitabine in the treatment of early breast cancer, looking at capecitabine-taxane combinations, capecitabine maintenance therapy, capecitabine for elderly patients, and sequential versus combination therapy, involving >20,000 patients.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

Tumor-suppressing gene therapy.

Tumor-suppressor genes play pivotal roles in maintaining genome integrity and in regulating cell proliferation, differentiation, and apoptosis. Their loss-of-function mutations are related directly to tumorigenesis. Thus, use of tumor-suppressor genes as anticancer therapeutics has been investigated rigorously in both experimental and clinical researches. Transfer of various tumor-suppressor genes directly to cancer cells has been demonstrated to suppress tumor growth via induction of apoptosis and cell-cycle arrest and, in some cases, with evidence for bystander effects. Various studies also have shown that combination of tumor-suppressor gene therapy with conventional anticancer therapy can yield synergistic therapeutic benefits. Clinical trials with tumor-suppressor genes, especially the p53 gene, have demonstrated that the treatment is well tolerated, and; favorable clinical responses, including a pathologically complete responses, have been observed in a subset of patients with advanced disease or with cancers resistant to conventional therapy. Yet, current gene replacement approaches in cancer gene therapy must be improved if they are to have a broader clinical impact. Efficient systemic gene delivery systems will be required ultimately for treatment of metastatic disease. In this review, we have recently summarized achievements in tumor-suppressor gene therapy with a focus on the p53 gene.

Animals↗
PubMed2003

The role of gene therapy in combined modality treatment strategies for cancer.

Multimodality therapy has been widely used in cancer treatment for enhancing efficacy, reducing toxicity, and preventing or delaying development of resistance. However, as the difference in biochemical signals between normal and malignant cells is usually trivial, combinations of conventional therapies often cause intolerably high levels of toxicity in most cancer patients. Gene therapy uses genetically encoded functions to attack molecular events involved in the development and maintenance of malignancies, providing a molecular approach to eradicate cancer cells or to protect normal cells from the toxicity of conventional therapies. Furthermore, gene therapy can also be used to augment biochemical signals required for effective chemotherapy and radiotherapy. Recent preclinical studies have shown that synergistic effects can be achieved by combining gene therapy and conventional anticancer therapies. Moreover, several phase I/II clinical studies have demonstrated that anticancer gene therapy is well tolerated and that combining gene therapy with chemotherapy, radiotherapy, or both, resulted in enhanced antitumor activity without increased toxicity. Favorable clinical responses, including a pathologically complete response, have been reported in a subset of patients with advanced disease or with cancers resistant to chemotherapy or radiotherapy. Thus, combining gene therapy and conventional therapies may provide an improvement in the treatment of cancers, especially for those resistant to conventional therapies. This review focuses on the most recent achievements in cancer treatment by combining gene therapy with conventional therapies.

Adenoviridae↗
PubMedDate not supplied

Activity of combination chemotherapy, docetaxel and epirubicin as neoadjuvant therapy for women with breast cancer.

BACKGROUND: This study assesses the efficacy of epirubicin and docetaxel as neoadjuvant therapy for women with breast cancer. PATIENTS AND METHODS: This is a single institution, single arm, phase II study of epirubicin given at 75 mg/m(2) and docetaxel at 75 mg/m(2) every three weeks for four cycles prior to surgical excision in women with large breast cancers. Pegfilgrastim was routinely administered as primary prophylaxis against febrile neutropenia. RESULTS: Out of the 18 patients enrolled on the study, 12 (66.7%) had a clinical response and 13 (72.2%) had a pathologic response, with a pathologic complete response of 5.6%. Pre-menopausal women and patients with estrogen receptor positive tumors had a higher response rate. One patient died due to sepsis and febrile neutropenia. CONCLUSION: Combination chemotherapy with epirubicin and docetaxel is highly active against breast cancer. With close monitoring for toxicity, this combination can be safely administered with mild side-effects.

Adult↗