A multicenter U.S. trial of neoadjuvant pemetrexed plus cisplatin (PC) followed by extrapleural pneumonectomy (EPP) and hemithoracic radiation (RT) for stage I-III malignant pleural mesothelioma (MPM)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7561-7561 ◽  
Author(s):  
L. M. Krug ◽  
H. Pass ◽  
V. W. Rusch ◽  
H. L. Kindler ◽  
D. Sugarbaker ◽  
...  
Keyword(s):  
Early Stage ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Early Time ◽  
Complete Response ◽  
High Rate ◽  
Vitamin Supplementation ◽  
Extrapleural Pneumonectomy ◽  
Eligibility Criteria ◽  
Trimodality Therapy

7561 Background: The optimal management for fit patients with early stage MPM remains controversial. One approach involves neoadjuvant chemotherapy followed by EPP and hemithoracic RT and prior trials using gemcitabine and cisplatin have been reported (Weder JCO 2004, Flores JTO 2006). We administered PC, followed by EPP and RT to further assess feasibility and survival of trimodality therapy in a larger, multicenter study. Methods: Eligibility criteria: Stage T1–3 N0–2, no prior surgical resection, adequate organ function (including predicted post-op FEV1 >35%) and PS 0–1. Pts received pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 with vitamin supplementation for 4 cycles. Pts without disease progression underwent EPP followed by RT (54 Gy). The primary endpoint was pathologic complete response (pCR) rate. Enrollment was completed in March, 2006. Results: 77 patients were enrolled and 72 are evaluable. Median age 63.5 (range 34–78), M:F = 51:21, Clinical stage I:II:III:IV = 5:31:33:1, epithelial:nonepithelial = 58:15, ECOG PS 0:1:2 = 28:42:2. 83% of patients completed all four cycles of PC. Grade 3/4 events related to chemotherapy included: neutropenia (4%), febrile neutropenia (3%), nausea (1%), vomiting (3%), pneumonia (6%), pulmonary embolism (1%), and chest pain (3%). Of 73 pts assessed for radiologic response, 3 CRs, 21 PRs, 36 SDs, 3 PDs, and 10 were unevaluable; (RR= 33% [95% CI, 0.22, 0.45]). Of 54 pts who underwent surgery, EPP completion rate was 87% (47/54); that is 47/77 (61%) by ITT. Pathologic stage I:II:III:IV:NE = 4:12:24:3:11. One pCR was confirmed. 35/39 completed RT. Preliminary TTP =13.1 mo (95% CI=9.6, 15.9; 48% censored) and median survival=16.6 mo (95% CI=13.9, 19.3; 55% censored;1-yr survival = 68%). Conclusions: This multicenter trial testing trimodality therapy in MPM showed that it is feasible with a high rate of chemotherapy delivery. One pCR was observed. Preliminary survival is below that reported by single institutions for patients undergoing EPP but with a high censorship rate at this early time point. Further analyses are necessary to identify a cohort of patients most likely to benefit. This study was sponsored by Eli Lilly & Company. No significant financial relationships to disclose.

Retrospective analysis of neoadjuvant chemoradiotherapy for esophageal cancer: The Knight Cancer Institute experience.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 126-126
Author(s):  
Faisal A Siddiqui ◽  
James P. Dolan ◽  
John G. Hunter ◽  
Miriam A. Douthit ◽  
Lisa M. Bloker ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Complete Remission ◽  
Early Stage ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Stage Ii ◽  
R0 Resection ◽  
Trimodality Therapy ◽  
Initial Staging

126 Background: Neoadjuvant chemoradiotherapy (NAT) followed by esophagectomy has been established as standard of care for early stage (II – III), resectable esophageal cancer (EC). Patients (pts) treated with NAT are more likely to be downstaged and have a complete (R0) resection. Additionally, pts with aggressive disease are more likely to progress during NAT and, consequently, avoid unnecessary surgery. The aim of the current report was to analyze the outcomes of trimodality therapy at the Knight Cancer Institute. Methods: A retrospective study of 124 pts who underwent NAT followed by esophagectomy for EC from 1999-2010 at our institution was performed. All pts were initially staged by imaging (EUS, CT and/or PET imaging) prior to commencing treatment. After esophagectomy, pathological staging was compared to initial staging to determine the effect of NAT. Results: There were 25 women and 99 men. Initial staging is shown in the table below. Patients received cisplatin, oxaliplatin or carboplatin with 5-FU plus concurrent radiotherapy (RT). RT total dose of 45 Gy to the tumor and regional nodes was given in 1.8 Gy daily fractions, followed by a boost to the tumor for final dose 50.4-54 Gy. 27 (21.8%) of the pts had a pathologic complete response. Additionally, 54 (43.6%) pts were downstaged by chemoradiation. Of the pts that had complete remission or were downstaged, pre-treatment clinical stage was Stage II (22 pts), Stage III (55 pts), and Stage IVa (4 pts). Conclusions: NAT was effective in complete remission or downstaging of two-thirds (81) pts, including 4 pts that were initially unresectable (Stage IVa) and successfully underwent subsequent esophagectomy. As has been shown previously, NAT is effective for downstaging prior to esophagectomy making it more likely that pts will undergo R0 resection. This study also demonstrated that some pts with clinically unresectable tumors could undergo successful esophagectomy after NAT. [Table: see text]

PrECOG 0105: Final efficacy results from a phase II study of gemcitabine (G) and carboplatin (C) plus iniparib (BSI-201) as neoadjuvant therapy for triple-negative (TN) and BRCA1/2 mutation-associated breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1003-1003 ◽  
Author(s):  
Melinda L. Telli ◽  
Kristin C. Jensen ◽  
Allison W. Kurian ◽  
Shaveta Vinayak ◽  
Jafi A. Lipson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Early Stage ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Breast Conservation ◽  
Complete Response ◽  
Pathologic Response ◽  
Residual Cancer Burden

1003 Background: TN and BRCA1-deficient breast cancer (BC) cell lines exhibit enhanced sensitivity to DNA damaging agents. This study was designed to assess efficacy, safety and predictors of response to iniparib in combination with GC in early-stage TN and BRCA1/2 mutation-associated BC. Methods: This single-arm, phase II study (NCT00813956) enrolled pts with clinical stage I-IIIA (T ≥ 1cm by MRI) ER-negative (≤ 5%), PR-negative (≤ 5%), and HER2-negative or BRCA1/2 mutation-associated BC. Neoadjuvant G (1000 mg/m2; IV; D1, 8), C (AUC 2; IV; D1, 8), and iniparib (5.6 mg/kg; IV; D1, 4, 8, 11) were given every 21 days for 4 cycles, until the protocol was amended to increase the treatment duration to 6 cycles, with enrollment of 80 pts at multiple PrECOG institutions. The primary endpoint is pathologic complete response (pCR), defined as no invasive carcinoma in the breast and axilla. Pathologic response was centrally assessed by the residual cancer burden (RCB) index. Assuming 76/80 eligible and treated pts, the regimen would be deemed effective if the lower bound of a 90% exact binomial CI on the pCR rate exceeded 25%. Secondary endpoints are safety, MRI response, and breast conservation. Results: Among 80 eligible pts treated with 6 cycles, median age is 48 years, 19 pts have germline BRCA1/2 mutations (90% tested to date) and clinical stage is I (13%), IIA (36%), IIB (36%), IIIA (15%). Pathologic response data (ITT population) are detailed below. 69 pts completed treatment per protocol: 5 progressed, 5 discontinued due to an AE and 1 mutation carrier was lost to follow-up. Most common G3/4 adverse events are neutropenia (49%), elevated ALT/AST (14%), and anemia (10%). Conclusions: Preoperative GC plus iniparib is active in the treatment of early-stage TN and BRCA1/2 mutation-associated BC. Clinical trial information: NCT00813956. [Table: see text]

scholarly journals Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation–Associated Breast Cancer With Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105

2015 ◽  
Vol 33 (17) ◽  
pp. 1895-1901 ◽  
Author(s):  
Melinda L. Telli ◽  
Kristin C. Jensen ◽  
Shaveta Vinayak ◽  
Allison W. Kurian ◽  
Jafi A. Lipson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Triple Negative ◽  
Phase Ii Study ◽  
Early Stage ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Predictors Of Response

Purpose This study was designed to assess efficacy, safety, and predictors of response to iniparib in combination with gemcitabine and carboplatin in early-stage triple-negative and BRCA1/2 mutation–associated breast cancer. Patients and Methods This single-arm phase II study enrolled patients with stage I to IIIA (T ≥ 1 cm) estrogen receptor–negative (≤ 5%), progesterone receptor–negative (≤ 5%), and human epidermal growth factor receptor 2–negative or BRCA1/2 mutation–associated breast cancer. Neoadjuvant gemcitabine (1,000 mg/m2 intravenously [IV] on days 1 and 8), carboplatin (area under curve of 2 IV on days 1 and 8), and iniparib (5.6 mg/kg IV on days 1, 4, 8, and 11) were administered every 21 days for four cycles, until the protocol was amended to six cycles. The primary end point was pathologic complete response (no invasive carcinoma in breast or axilla). All patients underwent comprehensive BRCA1/2 genotyping, and homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies. Results Among 80 patients, median age was 48 years; 19 patients (24%) had germline BRCA1 or BRCA2 mutations; clinical stage was I (13%), IIA (36%), IIB (36%), and IIIA (15%). Overall pathologic complete response rate in the intent-to-treat population (n = 80) was 36% (90% CI, 27 to 46). Mean HRD-LOH scores were higher in responders compared with nonresponders (P = .02) and remained significant when BRCA1/2 germline mutations carriers were excluded (P = .021). Conclusion Preoperative combination of gemcitabine, carboplatin, and iniparib is active in the treatment of early-stage triple-negative and BRCA1/2 mutation–associated breast cancer. The HRD-LOH assay was able to identify patients with sporadic triple-negative breast cancer lacking a BRCA1/2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. Confirmatory controlled trials are warranted.

Association of histologic grade and subtypes of gastric cancer (GC) with chemoradiation response.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 97-97
Author(s):  
Nikolaos Charalampakis ◽  
Graciela M. Nogueras-Gonzalez ◽  
Xuemei Wang ◽  
Elena Elimova ◽  
Hironori Shiozaki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Signet Ring Cell ◽  
Histologic Grade ◽  
Cancer Center ◽  
Trimodality Therapy ◽  
Signet Ring ◽  
Individualization Of Therapy

97 Background: Patients with localized gastric cancer (LGC), when treated with preoperative therapy, tend to have heterogeneous and unpredictable outcomes. Currently, no clinical variables or biomarkers can predict response. Methods: We analyzed 107 LGC patients who were treated with chemoradiation followed by surgery (trimodality therapy; TMT). Tumors were grouped into poorly (G3) or moderately (G2) differentiated and signet ring cell (SRC) or non-SRC histology. Association was made with pathologic complete response (pathCR) or < pathCR. Descriptive statistics and survival analyses were utilized. Results: The majority of the patients were male (60%), had clinical stage III cancer (51%), and received chemotherapy before chemoradiation (94%). All had adenocarcinoma and most had G3 (78%) and SRC histology (58%). PathCR was noted in 18% of patients with G3 and 33% of patients with G2 (p=0.125). Overall survival (OS) was significantly shorter for G3 patients compared to G2 patients (p=0.045). Patients with SRC histology had a lower rate of pathCR than those with non-SRC (8% vs 40%, p<0.001). Patients with SRC histology had a trend towards shorter OS (p=0.063). Surgical pathologic stage was independently associated with OS and recurrence-free survival (RFS) (p<0.001). Conclusions: Our data suggest that histologic grade/ subtypes are associated with response to preoperative chemoradiation. Independent validation and addition of biomarkers could allow individualization of therapy of LGC patients. From U. T. M. D. Anderson Cancer Center (UTMDACC), Houston, Texas, USA. (Supported in part by UTMDACC, and CA 138671 and CA172741 from the NCI). Dr. Nikolaos Charalampakis has been awarded a scholarship from the Hellenic Society of Medical Oncology.

Escalating and De-escalating Therapy for Early-Stage HER2-Positive Breast Cancer

2020 ◽  
pp. 3-13
Author(s):  
Danielle File ◽  
Giuseppe Curigliano ◽  
Lisa A. Carey
Keyword(s):  
Breast Cancer ◽  
Residual Disease ◽  
Early Stage ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Intrinsic Subtype ◽  
Her2 Positive ◽  
Drug Conjugates ◽  
Her2 Breast Cancer

Untreated, HER2+ disease is the most aggressive breast cancer phenotype; however, the development of multiple highly effective HER2-targeting drugs has transformed treatment and survival. These drugs include the anti-HER2 monoclonal antibodies trastuzumab and pertuzumab; small molecule inhibitors lapatinib, neratinib, and tucatinib; and antibody-drug conjugates trastuzumab emtansine (T-DM1) and now trastuzumab deroxtecan. More complex regimens using these drugs continue to improve outcomes, but the incremental benefits of these advances are often modest. Improved outcomes came from the addition of HER2-targeted therapies to conventional chemotherapy, beginning with trastuzumab, then pertuzumab added to trastuzumab, or with neratinib given for the year after trastuzumab. Neoadjuvant, or preoperative, administration of chemotherapy plus HER2-targeting allows surgical deescalation and tailoring treatment by pathologic complete response (pCR) to therapy. Patients with pCR after conventional therapy have excellent outcomes; what we now know is that the poorer outcomes associated with residual disease can be ameliorated with adjuvant T-DM1. However, as we have developed more complex, effective, and expensive therapy to maximize outcomes, it is also true that we are overtreating many patients. In stage I HER2+ breast cancer, there are excellent outcomes with paclitaxel plus trastuzumab or T-DM1 alone. Higher clinical stage HER2+ disease is still treated aggressively, although intrinsic subtype or activated immune tumor microenvironment may identify those with augmented treatment response or better outcome. It is likely that future strategies to escalate and de-escalate treatment with less chemotherapy, fewer anti-HER2 drugs, or shorter duration will depend upon integrated clinical and genomic modeling.

Factors Predictive of Distant Metastases in Patients With Breast Cancer Who Have a Pathologic Complete Response After Neoadjuvant Chemotherapy

2005 ◽  
Vol 23 (28) ◽  
pp. 7098-7104 ◽  
Author(s):  
Ana M. Gonzalez-Angulo ◽  
Sean E. McGuire ◽  
Thomas A. Buchholz ◽  
Susan L. Tucker ◽  
Henry M. Kuerer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Distant Metastases ◽  
Complete Response ◽  
Cox Regression Analysis

Purpose To identify clinicopathological factors predictive of distant metastasis in patients who had a pathologic complete response (pCR) after neoadjuvant chemotherapy (NC). Methods Retrospective review of 226 patients at our institution identified as having a pCR was performed. Clinical stage at diagnosis was I (2%), II (36%), IIIA (27%), IIIB (23%), and IIIC (12%). Eleven percent of all patients were inflammatory breast cancers (IBC). Ninety-five percent received anthracycline-based chemotherapy; 42% also received taxane-based therapy. The relationship of distant metastasis with clinicopathologic factors was evaluated, and Cox regression analysis was performed to identify independent predictors of development of distant metastasis. Results Median follow-up was 63 months. There were 31 distant metastases. Ten-year distant metastasis-free rate was 82%. Multivariate Cox regression analysis using combined stage revealed that clinical stages IIIB, IIIC, and IBC (hazard ratio [HR], 4.24; 95% CI, 1.96 to 9.18; P < .0001), identification of ≤ 10 lymph nodes (HR, 2.94; 95% CI, 1.40 to 6.15; P = .004), and premenopausal status (HR, 3.08; 95% CI, 1.25 to 7.59; P = .015) predicted for distant metastasis. Freedom from distant metastasis at 10 years was 97% for no factors, 88% for one factor, 77% for two factors, and 31% for three factors (P < .0001). Conclusion A small percentage of breast cancer patients with pCR experience recurrence. We identified factors that independently predicted for distant metastasis development. Our data suggest that premenopausal patients with advanced local disease and suboptimal axillary node evaluation may be candidates for clinical trials to determine whether more aggressive or investigational adjuvant therapy will be of benefit.

scholarly journals Durable Long-Term Remission With Chemotherapy Alone for Stage II to IV Laryngeal Cancer

2009 ◽  
Vol 27 (12) ◽  
pp. 1976-1982 ◽  
Author(s):  
F. Christopher Holsinger ◽  
Merrill S. Kies ◽  
Eduardo M. Diaz ◽  
Ann M. Gillenwater ◽  
Jan S. Lewin ◽  
...  
Keyword(s):  
Laryngeal Cancer ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Concurrent Chemotherapy ◽  
Stage Ii ◽  
High Rate ◽  
Disease Remission ◽  
Laryngeal Surgery ◽  
Platinum Based Chemotherapy

Purpose For patients with stage II to IV laryngeal cancer, radiation therapy (RT) either alone or with concurrent chemotherapy provides the highest rate of organ preservation but can be associated with functional impairment. Thus, we studied the use of induction chemotherapy with or without conservation laryngeal surgery (CLS). Our objectives were to study the sensitivity of laryngeal cancer to platinum-based chemotherapy alone and to highlight the efficacy of CLS in this setting. Patients and Methods Thirty-one previously untreated patients with laryngeal cancer (T2-4, N0-1, M0), who were resectable with CLS, were enrolled. Patients received three to four cycles of paclitaxel, ifosfamide, and cisplatin (TIP) chemotherapy, and response was assessed histologically. Patients with partial response (PR) proceeded to CLS. Patients achieving pathologic complete response (pCR) received an additional three cycles of TIP and no other treatment. Results Thirty patients were assessable for response. With TIP chemotherapy alone, 11 patients (37%) achieved pCR, 10 of whom (33%) remain alive with durable disease remission and no evidence of recurrence over a median follow-up time of 5 years. Nineteen patients (63%) treated with TIP alone achieved PR. The overall laryngeal preservation (LP) rate was 83%, and only five patients (16%) required postoperative RT. No patient required a gastrostomy tube or tracheotomy. Conclusion Chemotherapy alone in selected patients with T2-4, N0-1 laryngeal cancer can provide durable disease remission at 5 years. For patients with PR, CLS provides a high rate of LP. This prospective study suggests that chemotherapy alone may cure selected patients with laryngeal cancer, warranting further prospective investigation.

Phase II study of an epirubicin and docetaxel (ET) combination as pre and post-operative systemic therapy in patients with early stage breast cancer (EBC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10660-10660
Author(s):  
R. Nishimura ◽  
Y. Rai ◽  
S. Mitsuyama ◽  
S. Toyoshima ◽  
H. Iwasaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Response ◽  
Early Stage ◽  
Pathologic Complete Response ◽  
Metastatic Breast ◽  
Complete Response ◽  
Breast Conserving Surgery ◽  
Treatment Schedule ◽  
Primary Tumors ◽  
In Situ Carcinoma

10660 Background: The goal of chemotherapy (CT) for EBC is to achieve a high pathologic complete response (CR) leading to an increase in the rate of breast conserving surgery (BCS). ET is one of the most active CT regimens for metastatic breast cancer. The primary endpoint of this study was to evaluate clinical response Methods: Eligible patients (pts) were newly diagnosed with EBC and had large primary tumors (stage II-III, > 3 cm). Forty-seven pts were enrolled and received epirubicin 60 mg/m2 followed by docetaxel 60 mg/m2 every 3 weeks for 4 cycles before surgery. Within 4 weeks after surgery, 4 additional cycles of ET were given to the pts who responded to ET. Results: Forty-five pts were evaluable for safety and clinical response. The median age was 47 (range, 29–75). The tumor size was T2 in 44% of the pts, T3 in 36%, and T4 in 20%. ER and PgR were both positive in 40% of pts, while both negative in 31%. HER2 was positive in 33% of pts. Four cycles of ET at full dose were given to 96% of pts prior to surgery. The clinical response was 73% including 7% CR (95% CI 58–85%); the BCS rate was 36%. Central pathologic review was performed in 37 pts showing disappearance of all tumor cells (grade 1) in 1 patient (3%) and 2 pts (5%) achieved a grade 2 response (in situ carcinoma in the operated breast) by Chevallier’s criteria. Grade 3–4 toxicities included neutropenia (71%), leukocytopenia (69%), febrile neutropenia (18%) and anorexia (9%). Twenty-four of 33 pts who responded to ET received additional ET after surgery. Conclusions: ET showed a high clinical response in previously untreated EBC with acceptable toxicity. In order to improve pathological CRs further, the doses and treatment schedule of this regimen needs to be improved. Currently, we are following the pts to assess differences in survival between pts with or without additional adjuvant ET. No significant financial relationships to disclose.

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