Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “pathologic complete response”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources
PubMed2005

Phase III randomized trial of doxorubicin and docetaxel versus doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: an anglo-celtic cooperative oncology group study.

PURPOSE To compare the clinical and pathologic response rates of doxorubicin and cyclophosphamide (AC) with doxorubicin and docetaxel (AD) as primary chemotherapy in women with primary or locally advanced breast cancer. PATIENTS AND METHODS Eligible patients with histologically proven breast cancer with primary tumors >/= 3 cm, inflammatory or locally advanced disease, and no evidence of metastases were randomly assigned to receive a maximum of six cycles of either doxorubicin (60 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) administered intravenously (IV) every 3 weeks or doxorubicin (60 mg/m(2)) plus docetaxel (75 mg/m(2)) IV every 3 weeks, followed by surgery on completion of chemotherapy. Results A total of 363 patients were randomly assigned to AC (n = 180) or AD (n = 183). A complete clinical response was observed in 17% and 20% of patients treated with AC and AD, respectively (P = .42). Overall (complete and partial) clinical response rates for AC and AD were 61% and 70%, respectively (P = .06). There was no significant difference in either the pathologic complete response rates in the breast with AC (24%) and AD (21%; P = .61) or in the number of patients with positive axillary nodes at surgery with AC (61%) and AD (66%; P = .28). At a median follow-up of 32 months, there is no significant difference between the two groups for the number of relapses. CONCLUSION In contrast to the positive results reported for sequential docetaxel after AC as primary chemotherapy of breast cancer, our data do not suggest a benefit for simultaneous AD over AC.

Adult↗
PubMed2002

Treatment of hepatocellular carcinoma (HCC) with systemic chemotherapy combining epirubicin, cisplatinum and infusional 5-fluorouracil (ECF regimen).

PURPOSE: We tested the efficacy of a systemic chemotherapy regimen combining epirubicin, cisplatinum and infusional 5-fluorouracil (ECF) in a cohort of patients with hepatocellular carcinoma (HCC) who could not be given surgical, intraarterial or percutaneous treatment. PATIENTS AND METHODS: Between January 1998 and June 2000, 21 patients with metastatic and/or locally advanced HCC complicating a fibrous liver or a well-compensated (Child A) cirrhosis were given systemic chemotherapy with the ECF regimen. Tumor responses as assessed on CT scan and in terms of survival were studied. RESULTS: Patients completed a median of five chemotherapy courses. Overall tolerance was good but eight patients developed grade 3-4 toxicity, mainly hematological, and one patient experienced a grade 4 renal toxicity. Median survival was 10 months. Actuarial survivals (+/-SD) at 6 months, 1 year and 2 years were 90.2+/-9%, 70.3+/-10% and 24.6+/-19%, respectively. Of the 21 patients, 13 died, 12 from their tumor and 1 from treatment-related renal failure. There were only three objective responses (14.5%; CI95 1-28%) but one of these corresponded to a pathological complete response. The delay to tumor progression was 5.9+/-4.7 months. CONCLUSIONS: Systemic chemotherapy using the ECF regimen gave a poor response and low survival rates. It would appear reasonable to pursue the search for potentially efficacious chemotherapy protocols using other drug combinations.

Aged↗
PubMed2002

Efficacy of a primary chemotherapy regimen combining vinorelbine, epirubicin, and methotrexate (VEM) as neoadjuvant treatment in 89 patients with operable breast cancer.

PURPOSE: In order to improve the breast conservation rate for noninflammatory operable breast cancer stage II and IIIa, neoadjuvant chemotherapy containing vinorelbine, 25 mg/m(2), epirubicin, 35 mg/m(2), and methotrexate, 20 mg/m(2), VEM, was administered days 1 and 8 every 28 days for six cycles. METHODS: From October, 1991 to April, 1996, 89 patients (median age 52 years, range 31-72; 68 stage II and 19 stage IIIa) received 519 cycles (median six) of VEM chemotherapy. RESULTS: Hematotoxicity was mild (World Health Organization grade 3-4 neutropenia in 28% of cycles for 22 patients, and anemia or thrombocytopenia >grade 2) when it occurred, and there were no toxic deaths. The clinical objective response was 90% (28% complete response and 62% partial response). All patients underwent surgery: 77 (87%) had conservative and 12 (13%) had modified radical mastectomy, and 12 (14%) reached pathological complete response. At December, 2000, with a median follow-up of 86 months (39-100), 13 patients had relapsed, and five had died of metastatic disease. Median disease-free survival was 100 months (8.4 years) and median survival had not yet been reached.

Adult↗
PubMed1991

A comparison of hexamethylmelamine (altretamine), cyclophosphamide, doxorubicin, and cisplatin (H-CAP) vs. cyclophosphamide, doxorubicin, and cisplatin (CAP) in advanced ovarian cancer.

We retrospectively compared the results of treatment with hexamethylmelamine (HMM), cyclophosphamide, doxorubicin, and cisplatin (H-CAP) to treatment results using cyclophosphamide, doxorubicin, and cisplatin (CAP) in patients with advanced ovarian cancer. The treatments were identical in dosage and schedule with the exception of the addition of HMM to one regimen. Fifty-five patients treated with H-CAP between August 1977 and March 1980 were compared with a subsequent group of 22 patients who received CAP between October 1984 and October 1987. Following 6 months of therapy, patients were restaged either with second-look laparotomy or with clinical restaging. Fifty-three of 55 patients (96%) and 14/21 (67%) patients had objective responses to H-CAP and CAP respectively (p = 0.001). The pathologic complete response rate as determined by second-look laparotomy was higher in the patients who received H-CAP (35% vs. 19%). The median survival of patients receiving H-CAP is 47 months compared to 21 months for the CAP patients. In limited residual disease patients (maximum tumor diameter less than or equal to 3 cm), the median survival also favored the H-CAP treatment (101 months vs. 21 months, p = 0.002). The median time to progression was greater in patients receiving H-CAP vs. those receiving CAP (67 months vs. 16 months, p = 0.045). Treatment-related toxicity was similar for the two regimens. These findings suggest that the addition of HMM to CAP chemotherapy prolongs the median survival for patients with limited residual disease advanced ovarian cancer.

Altretamine↗
PubMed2006

A randomized double-blind placebo-controlled phase II trial of the cyclooxygenase-2 inhibitor Celecoxib in the treatment of cervical dysplasia.

OBJECTIVES: The objective of the study was to evaluate the efficacy of daily Celecoxib in the regression of moderate and severe cervical dysplasia, when compared to placebo. MATERIALS AND METHODS: Women, over the age of 18, with the histologic diagnosis of moderate or severe cervical dysplasia were enrolled in this IRB approved study. Women were randomized to receive either Celecoxib 200 mg twice a day or placebo. Both examining physician and patients were blinded to treatment option. Follow-up colposcopy with cervical cytology was obtained at 2-month intervals for 6 months, with cytologic and histologic specimens. RESULTS: From June 2002 until October 2003, a total of 25 patients were enrolled in this randomized phase II study. There was no statistical difference in screening entry criteria, clinical histologic and cytologic variables between the two groups. 60% of patients enrolled had an overall response in the trial. The mean time to response was 72 days. 75% of patients who received Celecoxib had a clinical response. This was significantly higher than the 31%, of the placebo patients that had a clinical response, P<0.03. 33% of patients in the Celecoxib group had complete pathologic response to therapy, which was higher than the placebo group 15%. CONCLUSION: We have observed that Celecoxib could have activity in the treatment of high-grade cervical dysplasia. As a result, medical treatment of cervical dysplasia with Celecoxib could offer a minimally invasive treatment with minor morbidity and time constraints. Further trials with larger numbers are needed to confirm these results.

Adult↗
PubMed2003

The addition of continuous infusion 5-FU to preoperative radiation therapy increases tumor response, leading to increased sphincter preservation in locally advanced rectal cancer.

PURPOSE: To compare the outcome from preoperative chemoradiation (CXRT) and from radiation therapy (RT) in the treatment of rectal cancer in two large, single-institutional experiences. PATIENTS AND METHODS: Between 1978 and 1995, 403 patients with localized, nonmetastatic, clinically staged T3 or T4 rectal cancer patients were treated with preoperative RT alone at two institutions. Patients at institution 1 (n = 207) were treated with pelvic CXRT exclusively, and patients at institution 2 were treated (except for 8 given CXRT) with pelvic RT alone (n = 196). In addition, a third group (n = 61) was treated with CXRT at institution 2 between 1998 and 2000 after a policy change. Both institutions delivered 45 Gy in five fractions as a standard dose, but institution 2 used 20 Gy in five fractions in selected cases (n = 26). At both institutions, concurrent chemotherapy consisted of a continuous infusion of 5-fluorouracil (5-FU) at a dosage of 1500 mg/m(2)/week. The end points were response, sphincter preservation (SP), relapse-free survival (RFS), pelvic disease control (PC), and overall survival (OS). RESULTS: Median follow-up was 63 months for all living patients at institution 1 and in the primary group of institution 2. Multivariate analysis of the patients in these groups showed that the use of concurrent chemotherapy improved tumor response (T-stage downstaging, 62% vs. 42%, p = 0.001, and pathologic complete response, 23% vs. 5% p < 0.0001), but did not significantly improve LC, RFS, or OS. Follow-up for the secondary group at institution 2 was insufficient to allow the analysis of these endpoints. In the subset of patients receiving 45 Gy who had rectal tumors < or /=6 cm from the anal verge (institution 1: n = 132; institution 2 primary: n = 79; institution 2 secondary: n = 33), there was a significant improvement in SP with the use of concurrent chemotherapy (39% at institution 1 compared with 13% in the primary group at institution 2, p < 0.0001). A logistic regression analysis of clinical prognostic factors indicated that the use of concurrent chemotherapy independently influenced SP in these low tumors (p = 0.002). This finding was supported by a 36% SP rate in the secondary group at institution 2. Thus SP increased after the addition of chemotherapy at institution 2. CONCLUSIONS: The use of concurrent 5-FU with preoperative radiation therapy for T3 and T4 rectal cancer independently increases tumor response and may contribute to increased SP in patients with low rectal cancer.

Academic Medical Centers↗
PubMed2005

Increased feasibility of weekly epirubicin and paclitaxel as neoadjuvant chemotherapy for locally advanced breast carcinoma.

BACKGROUND: Primary systemic therapy (PST) with a combination of epirubicin and paclitaxel achieves high response rates in locally advanced breast cancer (LABC), but considerable toxicity occurs and the patient's compliance is poor. In this open-label phase II trial toxicity of a weekly administration schedule was evaluated. PATIENTS AND METHODS: On days 1 and 8 of each 3-week cycle, 45 patients with non-inflammatory breast cancer received epirubicin (35 mg/m(2), intravenous bolus) followed by paclitaxel (80 mg/m(2) in 500 ml of normal saline infused over 3 h) for 3 cycles. Surgery was done 2 weeks after primary chemotherapy, followed by another 6 cycles of adjuvant CEF (cyclophosphamide 500 mg/m(2), epirubicin 70 mg/m(2), 5-fluorouracil 500 mg/m(2)) chemotherapy. RESULTS: The median tumor size before and after PST was 6.0 and 2.0 cm, respectively. The clinical response rate was 96%, including 24% complete remission; 5 patients (11%) achieved pathologically complete response (pCR) including 3 patients with carcinoma in situ. Only 5 (11%) patients underwent breast conserving surgery although there were 15 patients suitable. Axillary nodes were negative in 16 (36%) of the 45 patients. Febrile neutropenia was found in 1 patient. There was no severe cardiac toxicity or serious adverse events. CONCLUSIONS: PST with weekly epirubicin and paclitaxel was an effective and well-tolerated combination for LABC, although only few patients underwent breast conserving surgery.

Adult↗
PubMed1996

High-dose versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin in suboptimal ovarian cancer: a randomized study of the Gruppo Oncologico Nord-Ovest.

PURPOSE: The aim of the study was to compare high-versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin as primary chemotherapy for suboptimal stage III and IV ovarian cancer. PATIENTS AND METHODS: One hundred forty-five patients were randomized to receive six courses of cisplatin 50 or 100 mg/m2 plus epidoxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2. The two treatment arms were well balanced; all patients had greater than 2 cm and 37.2% had greater than 5 cm of residual disease; 29.6% had stage IV disease. RESULTS: Patients in the high-dose arm received a double dose-intensity and double total dose of cisplatin. The high-dose regimen induced significantly more episodes of leukopenia (47.8% v 32.8%, P = .05), thrombocytopenia (21.7% v 3.2%, P = .003), anemia (37.6% v 12.5%, P = .002), nephrotoxicity (six v one patient), and neurotoxicity (30.4% v 6.3%, P = .002). There were no significant differences in efficacy in terms of clinical response rate (high-dose 57.5% v low-dose 61.1%), pathologic complete response (CR) (9.6% v 18.1%), median survival times (29 v 24 months), and median progression-free survival (18 v 13 months). CONCLUSION: This study shows that doubling the dose-intensity and total dose of cisplatin in combination with epidoxorubicin and cyclophosphamide has significant toxic effects and does not improve clinical outcome in patients with suboptimal ovarian cancer.

Adult↗
PubMed2003

Neoadjuvant chemotherapy for cervical cancer.

None of the current surgical or radiation treatment strategies for cervical cancer satisfactorily leads to a high disease-free survival and a low risk for treatment-related complications in patients with bulky or locally-advanced disease. Neoadjuvant chemotherapy (NACT) prior to surgery or radiation therapy has been studied as a means to reduce tumour bulk and thereby rendering subsequent therapy more effective. Impressive clinical response rates to cisplatin-based NACT have been achieved with acceptable toxicity and survival. Of the patients treated, approximately 20% will achieve a complete clinical response and many of these patients will prove to have a complete pathological response. Although there are too few randomised controlled studies to determine the effectiveness of NACT approaches, relative to standard treatments.

Antineoplastic Agents↗
PubMed1996

[The efficacy of neoadjuvant chemotherapy and morphological classification of invasive bladder cancer according to chemoresponse].

BACKGROUND: We investigated the propriety of neoadjuvant chemotherapy and the possibility of bladder preservation based on clinical and pathological responses in invasive bladder cancer. METHOD: Nineteen cases of invasive bladder cancer which had been subjected to two courses of neoadjuvant chemotherapy followed by radical cystectomy were analyzed. RESULTS: The overall response rate was 79% (5/19), and 7 cases (37%) had a pathological complete response (pCR). Many cases showed degeneration or necrosis of cancer cells and infiltration of lymphocytes around the original cancer sites. Foamy macrophage or fibrous change was observed in high response cases. Thickening of the bladder wall were found after chemotherapy in such cases, which led to over-staging of the CT scan. We divided invasive bladder cancers into four different types based on gross tumor appearance and histology from TUR biopsy specimen: Type 1 which has an nodularly elevating pedunculated structure: Type 2A which has an elevating nonpedunculated structure with partly papillary component and no lymph vessel invasion: Type 2B which has an elevating nonpedunculated structure with partly papillary component and marked lymph vessel invasion: and Type 3 which has a nonelevating diffuse invasive structure with CIS lesion. The therapeutic effect was greater than grade 2 in 7 cases out of 8 (88%) Type 1, 2 cases out of 3 (67%) Type 2A, no case out of 6 (0%) type 2B, and 1 case out of 2 (50%) type 3. CONCLUSION: This classification will indicate the appropriate preoperative treatment for invasive bladder cancer, and will be useful when formulating criteria for bladder preservation. In particular, Type 1 or Type 2A is chemosensitive and may be considered for bladder preservation.

Adult↗
PubMed1994

Treatment of primary fallopian tube carcinoma with cisplatin-containing chemotherapy.

Because of the rarity of the primary fallopian tube carcinoma, optimal primary therapy is still not well defined, and there is little information available regarding the efficacy of combination chemotherapy in advanced disease. The experience obtained by treating 14 patients with fallopian tube carcinoma--most of them with advanced disease--using a combination of cisplatin, adriamycin, and cyclophosphamide (CAP) (10 patients) or carboplatin plus cyclophosphamide (4 patients) is reported. One patient had Stage Ic disease, 2 had Stage II, 9 had Stage III, and 2 had Stage IV. Eleven patients had clinically measurable disease (> 2 cm) at the start of chemotherapy. Eight of these patients had a complete clinical response (CR), 2 had partial response (PR), and 1 had progressive disease (PD). Of the 8 CR patients, 5 underwent second-look operation (SLO). Pathological complete response (pCR) confirmed in 4 out of 5 patients at SLO. The 3 patients without measurable disease (< 2 cm) after primary surgery had an indeterminate response to chemotherapy. Two of them (Stages Ic and II, respectively) had a negative SLO, while the third patient with Stage IV disease, who refused the SLO, remains disease-free 41+ months. This high response rate shows that this carcinoma is very responsive to cisplatin- or cisplatin analogue-containing regimens. One pCR and two clinical CR patients relapsed after 20, 14, and 16 months, respectively, from the completion of chemotherapy and died despite the second-line treatment. The toxicity of the regimens was moderate. The median survival was 40 months, and the actuarial 5-year survival rate was 48%. Carcinoma of the fallopian tube appears to respond favorably to cisplatin- or carboplatin-containing chemotherapy.

Adenocarcinoma↗
PubMed2001

Preoperative chemoradiotherapy and radical surgery for locally advanced distal rectal adenocarcinoma: pathologic findings and clinical implications.

PURPOSE: Preoperative chemoradiotherapy followed by radical surgical resection has been the preferred treatment for patients presenting with locally advanced distal rectal carcinoma at our institutions. We postulated that chemoradiotherapy-induced pathologic response of the primary tumor would identify which patients would be candidates for local excision as definitive surgical therapy. METHODS: A retrospective analysis of 60 patients with palpable, locally advanced, distal rectal adenocarcinomas treated from 1995 to 2000 was performed. All patients received preoperative chemoradiotherapy consisting of 5-fluorouracil (325 mg/m(2)) and leucovorin (20 mg/m(2)) by bolus infusion on Days 1 through 5 and 29 through 33 delivered concurrently with at least 45.0 to 50.4 Gy of pelvic radiation, followed six to eight weeks later by radical surgery and then adjuvant chemotherapy. RESULTS: Among 60 patients (20 females) there was a mean age of 58.7 (28-84) years. Clinical staging was as follows: Stage II, 14 patients (23 percent); Stage III, 35 patients (58 percent); and Stage IV, 11 patients (18 percent). Pathologic examination revealed that negative margins were obtained in 58 patients (97 percent). Downstaging to T0-2N0 was achieved in 17 patients (28 percent), with five (8 percent) achieving a pathologically complete response. Lymph nodes were positive in 24 patients (40 percent) despite chemoradiotherapy. Pathologic node positivity was found in 0 of 5 pT0 patients, 9 (41 percent) of 22 pT1 or pT2, and 15 (45 percent) of 33 pT3. Clinical stage, tumor size, pathologic stage, and adverse histologic features could not reliably predict pN0 status, except pT0 (5 patients only). CONCLUSIONS: Preoperative chemoradiotherapy often downsizes and downstages locally advanced rectal carcinoma. Neither pretreatment clinical characteristics, response to preoperative chemoradiotherapy, or pathologic features reliably predict pN0 status. Therefore, local excision is not recommended as an alternative to radical surgery for locally advanced adenocarcinoma of the distal rectum regardless of the response of the primary tumor to preoperative chemoradiotherapy.

Adenocarcinoma↗
PubMed1996

Induction chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (CAP) in a combined modality approach for locally advanced and inflammatory breast cancer. Long-term results.

Thirty-one patients with locally advanced and inflammatory breast carcinoma (stage IIIA and IIIB) were treated with a combined modality approach between 1985 and 1989. All patients received as induction chemotherapy a combination of cisplatin, doxorubicin, and cyclophosphamide (CAP). Responsive patients and patients with operable stable disease underwent modified radical mastectomy followed by concurrent radiotherapy and CMF (cyclophosphamide, methotrexate, 5-fluorouracil) adjuvant chemotherapy. Thirty patients were evaluable for response to CAP. The rate of objective response to induction chemotherapy was 76.7% with 2 patients (6.7%) obtaining a complete response and 21 patients (70%) a partial response. Twenty-five patients were rendered disease-free after induction chemotherapy and surgery. Only 2 of these had pathological complete response (8%). The median overall survival was 48.7 months, the median time to progression was 22.4 months and the median disease-free survival was 29.1 months. The patients with noninflammatory breast tumor had a significantly better overall survival, disease-free survival, and time to progression. The overall survival and the time to progression were statistically superior in patients with primary tumor size < or = 8 cm. At a median follow-up of 6 years, 29% (95% CI, 13.05 to 45.01) of patients were alive and 28% (95% CI, 10.4 to 45.6) were disease-free. This combined modality treatment seems feasible with quite acceptable toxicity; the CAP combination is an effective alternative to the other standard chemotherapeutic regimens. Our results, although encouraging, are still poor, and new drugs and strategies are required to improve the long-term outcome.

Adenocarcinoma↗
PubMed1986

A critical reassessment of second-look laparotomy in epithelial ovarian carcinoma.

Eighty-eight women with epithelial ovarian carcinoma, treated by first-line chemotherapy, achieved a complete clinical response and underwent second-look laparotomy to assess the true pathologic status of their disease. Persistent tumor was found in 50 patients (57%). Thirty-two of these (36%) had obvious gross tumor, whereas, 16 (18%) had microscopic disease. Thirty-eight patients (43%) had no pathologic evidence of persistent ovarian carcinoma. With a follow-up of 6 to 60 months, 30 of these patients (79%) remain without evidence of recurrence. Multivariate logistic regression analysis revealed three covariates that were independently significant in predicting continued disease-free status. These included: the greatest diameter of the largest residual tumor left at the primary operation; histologic features of the tumor; and the diameter of the largest tumor aggregate found at initial operation. A mathematical model based on the most significant covariates was designed to assess the relative risk of any patient having persistent tumor at second-look laparotomy. A comparison of the predicted to actual outcome revealed a sensitivity of the model of 88%, a specificity of 71%, and an accuracy of 77%. Second-look laparotomy represents the basis on which potentially curative second-line salvage therapy can be initiated. With an increasing period of follow-up and with greater numbers of patients, it can potentially document a complete pathologic response to first-line therapy administered with curative intent, and identify patients for additional, adjunctive therapy, who are at risk of recurrence.

Carcinoma↗
PubMed1996

Efficacy of up-front 5-fluorouracil-epidoxorubicin-cyclophosphamide (FEC) chemotherapy with an increased dose of epidoxorubicin in high-risk breast cancer patients.

The prognosis of patients with stage IIIB breast carcinoma with tumour spread to the apical axillary lymph nodes has hardly improved despite adequate locoregional control and the introduction of systemic adjuvant therapy. A combined modality regimen that includes anthracyclin-based chemotherapy, high-dose chemotherapy with peripheral stem cell support and radiation and hormonal therapy is currently under investigation in this subset of patients. The present study aims to document the efficacy and feasibility of dose-intensive epidoxorubicin in combination with a standard dose of 5-fluorouracil and cyclophosphamide as up-front chemotherapy in this setting. A preoperative chemotherapy regimen consisting of three courses of 5-fluorouracil 500 mg m-2, epidoxorubicin 120 mg m-2 and cyclophosphamide 500 mg m-2 (FE120C) was administered at 21 day intervals without haematopoietic growth factors to 70 patients with apex node-positive disease. All patients were below 60 years of age and had not had prior chemotherapy or radiotherapy. Sixty-six patients were evaluable for clinical response and histopathological examination could be performed in 62 of these. Thirteen patients achieved a clinical complete response (20%). Of these patients, microscopic examination of the mastectomy specimen revealed absence of malignant cells in two and exclusively ductal carcinoma in situ (DCIS) in another two patients. In addition, of the 46 patients (70%) with a clinical partial response, at pathological examination one patient had sclerosis only and four had DCIS. This results in a pathological complete response in three (5%) of all patients and absence of invasive carcinoma in 10%. None of the patients progressed during chemotherapy. The major toxicity was moderate bone marrow suppression with a median white blood count (WBC) nadir of 1800 microliters-1 (range 500-4900). Other toxicities were mild. The full planned dose could be given without delays in 66 of 70 patients FE120C is well tolerated and is highly effective as up-front chemotherapy in relatively young patients with high-risk breast cancer, with a 90% (CI 74-98%) clinical objective response rate.

Adult↗
PubMed1999

[Simultaneous radiochemotherapy with taxol/carboplatin in advanced operable head-neck tumors. Preliminary results].

BACKGROUND: The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrease the incidence of distant metastases. Regimens containing cisplatin/5-FU chemotherapy are widely accepted as standard treatment in advanced head and neck cancer. Most studies reported promising response and survival data, but also severe mucosal toxicity. In recent years the newly developed drug Taxol demonstrated interesting activity in head and neck cancer as a single agent and as well in combination drug regimens. In the present outpatient phase-II trial we investigated the combination of Taxol/carboplatin with 40 Gy radiotherapy in a neoadjuvant setting of operable Stage-III/IV squamous cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Twelve patients were enrolled in this ongoing trial with a projected number of 30 patients and received 5 cycles of weekly Taxol (40 mg/m2) and carboplatin (AUC 1.5) with conventional radiotherapy (40 Gy). Within 3 to 4 weeks after chemoradiotherapy resection of the primary tumor and the regional neck nodes was performed. RESULTS: So far 12 patients were evaluable for toxicity and response. Complete response was noted in 8/12 patients (CR 66%). In 6/10 patients (60%) complete pathologic response was documented in the resection specimens. CONCLUSION: Our preliminary results demonstrated excellent clinical and pathological response rates of concurrent Taxol/carboplatin and radiotherapy as preoperative treatment modality in advanced oral and oropharyngeal cancer.

Adult↗
PubMed1998

Preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, and sphincter preservation.

PURPOSE: To evaluate whether or not an intermediate dose of preoperative external radiation therapy intensified by systemic chemotherapy could improve the tumor response, sphincter preservation, and tumor control. METHODS AND MATERIALS: Between March 1990 and December 1995, 83 consecutive patients with resectable extraperitoneal adenocarcinoma of the rectum were treated with preoperative chemoradiation: bolus i.v. mitomycin C (MMC), 10 mg/m2, Day 1 plus 24-h continuous infusion i.v. 5-fluorouracil (5FU) 1000 mg/m2, Days 1-4, and concurrent external beam radiotherapy (37.8 Gy). All but 2 patients had T3 disease. Surgery was performed 4-6 weeks after the end of chemoradiation. RESULTS: Total Grade 3-4 acute toxicity during chemoradiation was observed in 11 (13%) patients: hematological Grade 3 toxicity was recorded in 8 (10%) patients, and Grade 4 toxicity was recorded in 2 (2%) patients. Grade 3 diarrhea was seen in 2 (2%) patients. No patient had major skin or urological acute toxicity. Two patients had no surgery: 1 died before surgery from septic complications after Grade 4 hematological toxicity; 1 refused surgery and is still alive after 6 years. There was no postoperative mortality and the overall perioperative morbidity rate was 25%. The analysis of tumor response involved 81 patients. Overall, 9% (7) of 81 patients had a complete pathologic response. Comparing the stage at the diagnostic workup with the pathologic stage, tumor downstaging was observed in 46 (57%) patients. We had 7 (9%) pT0, 5 (6%) pT1, 33 (41%) pT2, and 36 (44%) pT3. Nodal status downstaging was detected in 46 patients (57%). No evidence of nodal involvement was observed in 59 patients (73%). The incidence of tumor response was affected significantly by the number of quarters of rectal circumference involved (p = 0.03) and, marginally, by the length of the tumor (p = 0.09). The distance between the lower pole of the tumor and the anorectal ring had no influence. Of the patients, 63 (78%) had a sphincter-saving surgical procedure. In 12 (44%) of 27 patients candidate for an APR, the sphincter was preserved, as it was in 19 (95%) of 20 probable candidates. Lengthening of the distance between the anorectal ring and the lower pole of the tumor > 20 mm was observed in 21 patients (26%). Of 63 patients, 4 (6%) had moderate soilage after the sphincter-saving procedure. CONCLUSION: Preoperative combined modality therapy seems to afford some potential advantages in nonrandomized trials: patients are able to tolerate higher chemotherapy doses and they experience a lower acute toxicity. Tumor downstaging and resectability rates are high; sphincter preservation is feasible. Larger T3 tumors remained less influenced by this treatment; thus, taking into account the low toxicity rate recorded, a more aggressive schedule should be applied in these resectable tumors.

Adenocarcinoma↗
PubMed1997

p53 alterations are predictive of chemoresistance and aggressiveness in ovarian carcinomas: a molecular and immunohistochemical study.

Chemotherapeutic management of ovarian cancers is a difficult task as these neoplasms show significant differences in chemosensitivity, even if they share identical clinicopathological features. The present study was undertaken to investigate the prognostic and predictive role of p53 alterations in ovarian cancer. To this end, using different technical approaches, i.e. genetic and immunohistochemical analyses, we analysed a series of 68 ovarian neoplasms including 15 low malignant potential (LMP) tumours and 53 invasive carcinomas. We never observed p53 abnormalities in LMP tumours. p53 alterations were present only in invasive ovarian carcinomas, and they were detected much more frequently in tumours characterized by high histological grade (P = 0.01) and advanced-stage disease (P = 0.006 and P = 0.05 for gene mutations and protein expression respectively). For 33 patients with invasive ovarian cancer, information was available concerning response to cisplatin-based chemotherapy. A strong correlation (P = 0.001) has emerged between p53 alterations and response to chemotherapy; only one (14%) of seven patients who had a pathological complete response to antiblastic drugs showed p53 aberrations, whereas 18 (82%) of 22 cases with partial response and all of the four non-responsive patients scored positive for p53 abnormalities. We also observed that patients with p53 mutations had a significantly shorter progression-free survival than patients with p53-negative tumours (P = 0.05). Taken together, our results strongly suggest that in epithelial ovarian malignancies tumours showing p53 aberrations are significantly less sensitive to chemotherapy and more aggressive than those with functional p53. Thus, a routine analysis of this gene could have profound implications for the treatment of ovarian cancer.

Antineoplastic Agents↗