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Results for “Pathologic response”

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At least 577 records · Page 32Linked to original sources

PubMed2006

A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma.

PURPOSE: Concurrent chemotherapy and radiation therapy (RT) are used to treat patients with esophageal cancer. The optimal combination of chemotherapeutic agents with RT is undefined. We evaluated a combination of capecitabine, carboplatin, and paclitaxel with RT in a phase I study. METHODS AND MATERIALS: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus initially received capecitabine, carboplatin, and paclitaxel with RT (1.8 Gy daily to 50.4 Gy). After completion, patients were restaged and evaluated for surgery. Primary endpoints included determination of dose-limiting toxicities (DLT) and a recommended phase II dose, non-DLT, and preliminary radiographic and pathologic response rates. RESULTS: Thirteen patients were enrolled (10 men, 3 women). All were evaluable for toxicity and efficacy. Two of 3 patients at dose level 1 (capecitabine 825 mg/m(2) twice daily on RT days, carboplatin area under the curve (AUC) 2 weekly, paclitaxel 60 mg/m(2) weekly) had DLT (both Grade 4 esophagitis). Of these 3, 2 underwent esophagectomy and had pathologic complete response (pCR). Ten patients were then enrolled at dose level -1 (capecitabine 600 mg/m(2) twice daily, carboplatin AUC 1.5, paclitaxel 45 mg/m(2)). Overall, 3 of 10 patients at dose level -1 developed DLT (2 Grade 3 esophagitis, 1 Grade 3 hypotension). Esophagectomy was performed in 6 of 10 patients. All patients had pathologic downstaging and 2 of 6 had pCR. CONCLUSIONS: The maximally tolerated/recommended phase II doses were capecitabine 600 mg/m(2) twice daily, carboplatin AUC 1.5 weekly, and paclitaxel 45 mg/m(2) weekly with RT to 50.4 Gy. In our small study, this regimen appears active but is accompanied by significant toxicities, primarily esophagitis.

Adenocarcinoma↗

PubMed2004

Preoperative uracil, tegafur, and concomitant radiotherapy in operable rectal cancer: a phase II multicenter study with 3 years' follow-Up.

PURPOSE: To assess tolerance and efficacy of preoperative treatment with uracil/tegafur and radiotherapy (RT) followed by surgery and postoperative flurouracil (FU)/leucovorin (LV) in patients with rectal cancer. PATIENTS AND METHODS: Patients (n = 94) with potentially resectable tumors, ultrasound at stages T2N+ (n = 4), T3 (n = 77), T4 (n = 13) were treated with UFT (400 mg/m2/d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Patients underwent surgery 5 to 6 weeks later followed by four cycles of FU/LV. Primary end points included downstaging, pathologic responses, and sphincter-preserving surgery. Secondary end points were recurrence-free survival and overall survival. RESULTS: All patients received the full RT dose. Fifteen patients (16%) needed UFT dose reduction. Preoperative G3+ toxicities included diarrhea (14%), leukopenia (1%), thrombocytopenia (1%), and nausea (4%). The downstaging rate was 54%, pathologic complete response (pCR) was 9% and, in an additional 23%, there were only residual microscopic foci. When cellular viability criteria were taken into account, the pCR was 15%. From 43 patients with abdominoperineal resection indication, 11 (25%) had sphincter-preserving surgery performed. Postoperative scheduled chemotherapy dose was not administered to 24% of patients because of G3+ toxicity (diarrhea, 8%; mucositis, 9%; and leukopenia, 7%). Patients with downstaging had significantly higher survival and recurrence-free survival rates than those without. At 3 years, actuarial patterns of failure were pelvic, 5% and distant, 11%. OS was 75%. CONCLUSION: UFT combined with RT is safe and effective. In resectable rectal cancer, if preoperative treatment is considered, this approach can be an option.

Adenocarcinoma↗

PubMed2000

Preoperative chemotherapy for operable breast cancer.

In the NSABP B-18 study, it was demonstrated that, in patients with operable breast cancer, the administration of preoperative and postoperative chemotherapy resulted in similar DFS and overall survival outcomes. In addition, preoperative chemotherapy resulted in high clinical response rates but in low rates of pathologic response in the breast. Axillary nodal downstaging was convincingly demonstrated. In addition, it was also demonstrated in B-18, as well as in other studies, that there was an increase in breast conservation rates after the administration of preoperative chemotherapy. The role of preoperative chemotherapy for operable breast cancer continues to be evaluated in randomized trials, which have the potential of providing further insight into the biologic and clinical questions relative to the timing of adjuvant therapy for the disease.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

The role of radical hysterectomy and neoadjuvant chemotherapy in carcinoma of the cervix.

The patient presenting with a bulky stage IB2 cervical cancer is a therapeutic challenge. None of the current surgical or radiation treatment strategies satisfactorily leads to a high rate of disease-free survival and a low risk of treatment-related complications including ovarian failure and psychosexual deficits. Neoadjuvant chemotherapy may allow for reductions in tumor bulk, thereby rendering radiation therapy more effective or surgery more feasible. Impressive clinical response rates to cisplatin-based neoadjuvant chemotherapy have been achieved with acceptable toxicity. Approximately 20% of patients achieve a complete clinical response, and many also experience a complete pathologic response. There are still too few comparative studies and phase III trials to assess the effectiveness of neoadjuvant chemotherapy and radical surgery relative to standard treatments.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Neoadjuvant combined chemotherapy followed by external whole pelvic irradiation in two cases of primary extranodal non-Hodgkin's lymphoma of the uterine cervix.

BACKGROUND: Primary extranodal lymphomas of the genital tract are rare. CASES: As there is no current consensus in its management, we present two further cases and their treatment with neoadjuvant chemotherapy, followed by radiation therapy. A radical hysterectomy with bilateral pelvic lymphadenectomy was performed after primary treatment in one case. Clinical response was complete in both cases and pathological response was documented in one. CONCLUSIONS: Complete response of these lymphoid neoplasms can be achieved by neoadjuvant chemotherapy followed by external irradiation.

Adult↗

PubMed1994

Toward a training model for Rorschach scoring revisited: a follow-up study on a training system for interscorer agreement.

A standardized method for training in Rorschach scoring using the Perceptanalytic system showed high interscorer reliability in a classroom setting by 1984. To assess whether this model for training would continue to yield stronger interscorer agreement with continued use in vivo data from classroom training were gathered over a six-year follow-up period (1985-1991). For the subjects, 167 students in a graduate clinical psychology training program, results indicated the system produces high interscorer agreement at both Level I (relatively clear and simple responses) and Level II (very complex or pathological responses). Over-all percent of agreement for 54,329 combined coding and summarizing operations attained a M of 90% (SD = 6.0%). Sufficiently high interscorer reliability in Rorschach scoring can be attained in a classroom setting to support the use of the Perceptanalytic method for training doctoral students. Further research on training systems for the Rorschach as well as some speculative heuristic hypotheses about the nature of the learning process for Rorschach scoring are suggested.

Adult↗

PubMed2001

Comparative study of bulky stage IB and IA cervical cancer patients treated by radical hysterectomy with and without neoadjuvant chemotherapy: long-term follow-up.

One hundred and ninety patients with bulky (> 3 cm) stage IB and IIA cervical cancer who underwent radical hysterectomy between 1991 and 1994 at Maharaj Nakorn Chiang Mai Hospital were reviewed to determine whether neoadjuvant chemotherapy (NAC) with MVAC (Methotrexate, Vinblastine, Adriamycin, Cisplatin) improved survival. There were 42 patients treated with pre-operataive NAC (MVAC 1-3 courses) and 148 patients treated by primary surgery (PS). In the NAC group, the overall response rate from MVAC was 88.1 per cent with 31.0 per cent having complete clinical response and 7.1 per cent with complete pathological response. Pelvic lymph node metastasis was not significantly different between the NAC group (16.7%) and the PS group (18.2%). At a median follow-up of 64.5 months, 19.0 per cent in the NAC group and 18.2 per cent in the PS group had tumor recurrence. The 5-year progression free and overall survival was 80.8 per cent and 92.0 per cent respectively for the NAC group which was not significantly different from 80.2 per cent and 92.9 per cent respectively in the PS group. In conclusion, although NAC can decrease the tumor size and produce a high response rate, it does not improve survival in bulky stage IB and IIA cervical cancer patients.

Adenocarcinoma↗

PubMedDate not supplied

Weekly chemotherapy with cisplatin and paclitaxel in inoperable non-small cell lung cancer: an extended phase II study.

BACKGROUND: A phase II study of a cisplatin/paclitaxel combination given on a weekly schedule in the front-line treatment of non-small cell lung cancer (NSCLC) is reported. PATIENTS AND METHODS: Treatment consisted of an intravenous infusion of cisplatin, 25 mg/m2, and paclitaxel, 80 mg/m2, every week. Chemotherapy was continued until completion of a 22-week treatment plan, disease progression, persistent toxicity, or patient refusal. RESULTS: Seventy-nine patients entered the study. The median number of infusions per patient was 14 (range 0-22). The median dose-intensity was 75% of that projected. Toxicity was generally acceptable, and never life-threatening. Seven complete responses (pathologically documented in 4 patients) and 27partial responses were observed for an overall response rate of 43%. The estimated median survival and median time to progression was 55 (95% CI: 38-71) and 37 weeks (95% CI: 31-44), respectively. CONCLUSION: In our experience, the weekly combination of cisplatin and paclitaxel is well tolerated, active and associated with remarkably long survivals.

Adult↗

PubMed1995

Role of proinflammatory cytokines in acetaminophen hepatotoxicity.

Acetaminophen (APAP) intoxication has been shown to activate Kupffer cells. Kupffer cell activation is also associated with the release of proinflammatory cytokines which can induce a variety of pathophysiological responses. These studies examined whether proinflammatory cytokines are produced in response to a hepatotoxic dose of APAP, and if so, the role they play in the observed pathological response. Female B6C3F1 mice received 500 mg APAP/kg in the presence and absence of antibodies against tumor necrosis factor-alpha (TNF-alpha), interleukin-1-alpha (IL-1 alpha), and IL-1 receptor antagonist (IL-1ra). Serum TNF-alpha, IL-1 alpha, and liver-associated enzyme levels were measured. In addition, the levels of mRNA transcripts for IL-1 alpha, IL-6, and TNF-alpha from livers of treated mice were examined by reverse transcription-polymerase chain reaction (RT-PCR). Administration of APAP resulted in an immediate reduction in body temperature as well as elevated serum levels of IL-1 alpha and TNF-alpha that reached a peak at 12 and 16 hr, respectively. The reduction in body temperature was partially blocked by injection of antibodies against TNF-alpha or IL-1 alpha. Furthermore, neutralization of TNF-alpha delayed the increase in serum IL-1 alpha and liver enzyme levels. In contrast, pretreatment with IL-1ra antisera exacerbated the effect of APAP on body temperature and increased the release of liver enzymes. These data suggest that TNF-alpha and IL-1 alpha are released in response to APAP intoxication and are responsible for certain pathological manifestations of APAP-induced hepatotoxicity.

Acetaminophen↗

PubMed2004

Pulmonary resection after curative intent radiotherapy (>59 Gy) and concurrent chemotherapy in non-small-cell lung cancer.

BACKGROUND: Pulmonary resection after chemotherapy and concurrent full-dose radiotherapy (>59 Gy) has previously been associated with unacceptably high morbidity and mortality. Subsequently neoadjuvant therapy protocols have used reduced and potentially suboptimal radiotherapy doses of 45 Gy. We report a series of 40 patients with locally advanced non-small-cell lung cancer who successfully underwent pulmonary resection after receiving greater than 59 Gy radiation and concurrent chemotherapy. Operative results and midterm survival follow-up are presented. METHODS: Data were reviewed from 40 consecutive patients who underwent lung resection after receiving high-dose radiotherapy and concurrent platinum-based chemotherapy between January 1994 and May 2000. The follow-up closing interval for this study was until August 2003 or time of death. RESULTS: Preoperative stage was IIb (7 patients), IIIA (21 patients), IIIB (10 patients), and IV (2 patients with isolated brain metastasis). Thirteen patients exhibited Pancoast tumors. Median time from completion of induction therapy to surgery was 53 days. Twenty-nine lobectomies and 11 pneumonectomies (7 right, 4 left) were performed. There were no postoperative deaths. Intercostal muscle flaps were used prophylactically in all but one pneumonectomy patient. Seven patients required perioperative transfusions. Median intensive care unit (ICU) time averaged 2 days and the total length of stay was 6 days. One patient exhibited postpneumonectomy pulmonary edema and a bronchopleural fistula developed in another patient (not receiving an intercostal muscle flap). Thirty-four of 40 patients (85%; 95% CI: 70%-94%) were downstaged pathologically, 33 out of 40 patients (82.5%, 95% confidence interval [CI]: 67%-93%) indicated no residual lymphadenopathy, and 18 out of 40 patients (45%, 95% CI: 29%-61%) exhibited a complete pathologic response. Median follow-up was 2.8 years. The 1-, 2-, and 5-year overall survival rates were 92.4%, 66.7%, and 46.2%, respectively. Disease-free 1-, 2-, and 5-year survival rates were 73.0%, 67.2%, and 56.4%, respectively. Median disease-free survival has not been reached. CONCLUSIONS: Pulmonary resection may be performed safely after curative intent concurrent chemotherapy and radiotherapy to greater than 59 Gy. High pathologic complete response rates and sterilization of mediastinal lymph nodes were observed accompanied by highly favorable survival rates. This experience, though promising, will require confirmation in a prospective multiinstitutional clinical trial.

Adult↗

PubMed2000

Phase II evaluation of preoperative chemoradiation and postoperative adjuvant chemotherapy for squamous cell and adenocarcinoma of the esophagus.

PURPOSE: This phase II trial evaluated continuous-infusion cisplatin and fluorouracil (5-FU) with radiotherapy followed by esophagectomy. The objectives of this trial were to determine the complete pathologic response rate, survival rate, toxicity, pattern of failure, and feasibility of administering adjuvant chemotherapy in patients with resectable cancer of the esophagus treated with preoperative chemoradiation. PATIENTS AND METHODS: Patients were staged using computed tomography, endoscopic ultrasound, and laparoscopy. The preoperative treatment plan consisted of continuous intravenous infusion of cisplatin and 5-FU and a total dose of 44 Gy of radiation. Esophagogastrectomy was planned for approximately 4 weeks after the completion of chemoradiotherapy. Paclitaxel and cisplatin were administered as postoperative adjuvant therapy. RESULTS: Forty-two patients were enrolled onto the trial. Of the 39 patients who proceeded to surgery, 29 responded to preoperative treatment: 11 achieved pathologic complete response (CR) and 18 achieved a lower posttreatment stage. Five patients had no change in stage, whereas eight had progressive disease (four with distant metastases and four with increases in the T and N stages). At a median follow-up of 30.2 months, the median survival time has not been reached and the 2-year survival rate is 62%. The median survival of pathologic complete responders has not been reached, whereas the 2-year survival rate of this group is 91% compared with 51% in patients with complete tumor resection with residual tumor (P =.03). CONCLUSION: An excellent survival rate, comparable to that of our prior preoperative trial, was achieved with lower doses of preoperative cisplatin and 5-FU concurrent with radiotherapy.

Adenocarcinoma↗

PubMed1996

Combined preoperative chemotherapy and radiotherapy in patients with locally advanced esophageal cancer. Interim analysis of a phase II trial.

PURPOSE: The prognosis of patients with locally advanced esophageal cancer (LAEC) remains poor when treated with local modalities. An intensive preoperative program with chemoradiotherapy was used to evaluate the curative resection rate, pathologic response, and survival of patients with LAEC. PATIENTS AND METHODS: Ninety patients with LAEC were treated preoperatively with chemotherapy (three courses of fluorouracil, leucovorin, etoposide, and cisplatin [FLEP]) followed by concurrent chemoradiotherapy (one course of cisplatin plus etoposide in combination with 40 Gy of radiation). Transthoracic esophagectomy was performed 4 weeks after the end of radiation. RESULTS: Seventy-two patients were included in this evaluation. Forty-four (61%) underwent a complete tumor resection, and 16 (22%) had no tumor in the resected specimen (pathologic complete response [PCR]). The operative mortality rate was 15%. At a median follow-up time of 22 months (range, 12 to 41), the median survival duration of all 72 patients was 17 months (range, 1 to 41+). The calculated survival rates at 3 years were 33%, 42%, and 68% for all patients, patients after complete resection, and patients with PCR, respectively. CONCLUSION: This combined treatment modality is active in LAEC, with a PCR in 33% of the patients undergoing surgery. The results appear improved compared with those reported with surgery alone, by approximately doubling the 3-year survival rate. The high efficacy of preoperative chemoradiation warrants evaluation of the role of surgery in LAEC.

Adenocarcinoma↗

PubMed2006

Improved incidence of pT0 downstaged surgical specimens in locally advanced rectal cancer (LARC) treated with induction oxaliplatin plus 5-fluorouracil and preoperative chemoradiation.

PURPOSE: To compare efficacy in terms of pathologic response in LARC patients treated with preoperative chemoradiation, with or without a short-intense course of induction oxaliplatin. PATIENTS AND METHODS: From 05/98 to 10/02, 114 patients were treated with preoperative chemoradiation (4500-5040 cGy + oral Tegafur 1200 mg/day) for cT(3)-(4)N(+/x)M(0) rectal cancer. Starting 05/01, 52 consecutive patients additionally received induction FOLFOX-4, oxaliplatin (85 mg/m(2) iv d1), 5-FU (400 mg/m(2) iv bolus d1) and 600 mg/m(2) iv continuous infusion in 22 h with leucovorin (200 mg iv) d1 and d2, every 15 days (2 cycles), followed by the previously described Tegafur chemoradiation regime. Surgery was performed in 5-6 weeks. Pathological assessment investigated post-treatment T and N status in the rectal wall and peri-rectal tissues. RESULTS: Patients, tumor and treatment characteristics were comparable between groups. Incidence of pT(0) specimens was significantly increased by induction FOLFOX-4 (P = 0.006). Total T and N downstaging were 58% versus 75% and 42% versus 40%, respectively (P = ns). T downstaging of > or =2 categories was significantly superior in FOLFOX-4 group (P = 0.029). CONCLUSIONS: Short-intense induction FOLFOX-4 significantly improves pathologic complete response in LARC patients treated with tegafur-sensitized preoperative chemoradiation. The 44% rate of pT(0)-(1) specimens observed in the oxaliplatin group should impulse innovative surgical approaches to promote ano-rectal sphincter conserving protocols.

Adult↗

PubMed1994

Neoadjuvant chemotherapy for invasive bladder carcinoma: disease outcome and bladder preservation and relationship to local tumor response.

Thirty-nine patients with locally advanced transitional cell carcinoma of the bladder received presurgical combination chemotherapy in an effort to improve survival, reduce local tumor recurrence and distant failure, and enhance surgical resectability and potentially salvage the bladder. One to six cycles (median 2.8) of M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin), CMV (cisplatin, methotrexate, vinblastine), or VP16 CDDP (etoposide, cisplatin) were administered after initial diagnosis and clinical staging of the bladder cancer and transurethral resection of the tumor. Clinical staging was repeated before each cycle of chemotherapy. Transurethral resection and systemic neoadjuvant chemotherapy clinically downstaged 31 of 39 patients (79%). Subsequently, 26 patients underwent radical cystectomy and 13 patients received bladder salvage (6 received a partial surgical resection and 7 observation). At 41 months' median follow-up, 4-year overall survival was 63 +/- 17%, cancer-specific survival was 71 +/- 19%, local recurrence-free survival was 66 +/- 22%, and metastasis-free survival was 73 +/- 16%. Patients with a complete clinical and pathologic response had far better survival than those without a complete response; for pathologic stage, survival was 100% vs. 45% for those with residual tumor (p = 0.003). Local recurrence (Ta or TiS) occurred in 46% of those with their bladder salvaged and still in situ. These data suggest that with neoadjuvant chemotherapy bladder salvage seems feasible in selected patients, although they appear to be at higher risk for tumor recurrence. Accurate selection of the group of patients most likely to benefit is difficult and may not be possible in a predictable manner with currently available selection methods.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

High-dose platinum versus standard dose in advanced ovarian carcinoma: a randomized trial from the Gynecologic Cooperative Group of the French Comprehensive Cancer Centers (FNCLCC).

OBJECTIVE: The aim of this study was to evaluate the impact of platinum dose intensity on pathological response rate and overall survival in patients with advanced ovarian adenocarcinoma. METHODS: Between February 1992 and December 1996, 195 previously untreated patients with FIGO stage IIb-c, IIIb-c, or IV with macroscopic residual disease after suboptimal debulking surgery were randomized to receive CCC (100 mg/m(2) of cisplatin, 300 mg/m(2) of cyclophosphamide, 300 mg/m(2) of carboplatin, n = 96) or CC (100 mg/m(2) of cisplatin, 600 mg/m(2) of cyclophosphamide, n = 99) for six courses at 28-day intervals. A second-look laparotomy was planned at the end of chemotherapy. RESULTS: In the CCC arm, the platinum compound received dose intensity and relative total dose were 85 and 76%; in the CC arm, they were 94 and 85%. Grade 3-4 toxicity was more frequent in the CCC arm than in the CC arm for leukopenia (56% vs 26%, P < 0.001), febrile neutropenia (18% vs 4%, P = 0.002), anemia (31% vs 5%, P < 0.001), thrombopenia (55% vs 4%, P < 0.001), and ototoxicity (8% vs 0%, P < 0.001). The pathologic complete response rate was 22 and 14% in the CCC and CC arms, respectively (P = 0.19). With a median follow-up of 53 months, the median time to failure and the 3-year treatment failure-free survival rate were 17.4 months and 22% vs 13 months and 11% in the two arms, respectively (P = 0.01). The median survival time and the 3-year overall survival rate were, respectively, 30 months and 42% vs 25 months and 33% (P < 0.20). CONCLUSION: The platinum dose intensification (1.6-fold increase) obtained with the CCC association improves the treatment failure-free survival without significant impact on overall survival when compared with the CC regimen in suboptimal debulked ovarian adenocarcinoma. However, because of its high rate of hematologic toxicity and ototoxicity, this association cannot be recommended for routine practice.

Adenocarcinoma↗

PubMed1983

Disorders of stimulus-response coupling in neutrophils.

The initiation of both the normal and pathologic responses of human neutrophils to surface stimulation and the ensuing biochemical and physiologic events are elucidated. This knowledge has contributed to an understanding of the controlling mechanisms that may account for impaired phagocytic function in several clinical disorders associated with recurrent bacterial infections.

Animals↗

PubMed1999

1-Aminoindan-1,5-dicarboxylic acid and (S)-(+)-2-(3'-carboxybicyclo[1.1.1] pentyl)-glycine, two mGlu1 receptor-preferring antagonists, reduce neuronal death in in vitro and in vivo models of cerebral ischaemia.

Metabotropic glutamate (mGlu) receptors have been implicated in a number of physiological and pathological responses to glutamate, but the exact role of group I mGlu receptors in causing postischaemic injury is not yet clear. In this study, we examined whether the recently-characterized and relatively selective mGlu1 receptor antagonists 1-aminoindan-1,5-dicarboxylic acid (AIDA) and (S)-(+)-2-(3'-carboxybicyclo[1.1.1]pentyl)-glycine (CBPG) could reduce neuronal death in vitro, following oxygen-glucose deprivation (OGD) in murine cortical cell and rat organotypic hippocampal cultures, and in vivo, after global ischaemia in gerbils. When present in the incubation medium during the OGD insult and the subsequent 24 h recovery period, AIDA and CBPG significantly reduced neuronal death in vitro. The extent of protection was similar to that observed with the nonselective mGlu receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine [(+)MCPG] and with typical ionotropic glutamate (iGlu) receptor antagonists. Neuroprotection was also observed when AIDA or CBPG were added only after the OGD insult was terminated. Neuronal injury was not attenuated by the inactive isomer (-)MCPG, but was significantly enhanced by the nonselective mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic acid [(1S,3R)-ACPD] and the group I mGlu receptor agonist 3,5-dihydroxyphenylglycine (3,5-DHPG). The antagonists (+)MCPG, AIDA and CBPG were also neuroprotective in vivo, because i. c.v. administration reduced CA1 pyramidal cell degeneration examined 7 days following transient carotid occlusion in gerbils. Our results point to a role of mGlu1 receptors in the pathological mechanisms responsible for postischaemic neuronal death and propose a new target for neuroprotection.

Animals↗

PubMed2001

Dose-dense doxorubicin, docetaxel, and granulocyte colony-stimulating factor support with or without tamoxifen as preoperative therapy in patients with operable carcinoma of the breast: a randomized, controlled, open phase IIb study.

PURPOSE: To investigate the effect of adding tamoxifen to a preoperative dose-dense doxorubicin and docetaxel regimen on the pathologic response of primary operable breast cancer. PATIENTS AND METHODS: Patients (tumor size > or = 3 cm, N0 to 2, M0) were prospectively randomized to receive every 14 days a total of four cycles of doxorubicin 50 mg/m2 and docetaxel 75 mg/m(2), either with (ADocT) or without (ADoc) simultaneous tamoxifen. Granulocyte colony-stimulating factor (G-CSF) was routinely given on days 5 to 10. Surgery followed 8 to 10 weeks after the start of treatment. RESULTS: Within 14 months, 250 patients were included in the study at 56 centers. Of 992 planned cycles, 97.9% were administered. Pathologically complete remission (pCR) with no detectable viable tumor cells was achieved in 9.7%. There was a nonsignificant difference of -1.2% in favor of ADoc, with a 95% confidence interval of -8.6% to 6.2%. A further 2.4% had only noninvasive tumor residues, and 13.8% had focal invasive residues. Complete and partial responses detected by palpation were observed in 28.9% and 52.4%, respectively. The response rates (complete and partial) by best appropriate imaging methods were 77.5% and 67.5% for ADocT and ADoc, respectively. Breast conservation was possible in 68.8% of the patients. A tendency toward more frequent toxic events was observed with ADocT treatment. Significant predictors of pCR to chemotherapy were negative lymph node and negative estrogen receptor status. CONCLUSION: A dose-dense regimen of ADoc with G-CSF offers high compliance, moderate toxicity, and rapid efficacy as a form of preoperative chemotherapy in operable breast cancer. Concurrent treatment with tamoxifen for 8 weeks could not improve the pathologic response rate.

Adult↗