Multiagent concurrent chemoradiotherapy (MACCRT) and gefitinib in locoregionally advanced head and neck squamous cell cancer (HNSCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6037-6037
Author(s):  
C. P. Rodriguez ◽  
D. J. Adelstein ◽  
J. P. Saxton ◽  
L. A. Rybicki ◽  
R. R. Lorenz ◽  
...  

6037 Background: In patients (pts) with stage III-IV HNSCC, MACCRT has led to excellent locoregional control. Distant metastases (DM) are now the most common cause of treatment failure. This phase II study tested whether the oral EGFR inhibitor gefitinib (G) added to our Cleveland Clinic MACCRT regimen would decrease DM and improve survival. Methods: Between 4/03 and 9/07, 60 previously untreated pts with stage III-IV (M0) HNSCC, and a performance status of <1 were enrolled on this study. Pts received hyperfractionated radiation (72–74.4 Gy at 120cGy bid) and concurrent chemotherapy with cisplatin (20 mg/m2/day) and fluorouracil (1,000 mg/m2/day), both given as 96-hour continuous IV infusions during weeks 1 and 4. G 250 mg daily was begun on day 1 of the radiation and continued for 2 years. The results were retrospectively compared to our previous study of 44 pts treated with the same MACCRT regimen without G between 1/96 and 9/00. Results: The study population included a preponderance of Caucasian (97%) males (88%) with stage IV (80%) oropharynx tumors (68%), and with a median age of 58 (range 24–75) years. Patient and tumor characteristics were similar to the non-G treated historical cohort. When comparing the G vs. non-G treated pts, acute toxicities including transient renal dysfunction (28% v. 5% p = 0.002) and all-cause re-hospitalization (83% v. 64%, p = 0.022) were worse. Myelosuppression was similar. G-specific toxicity included > grade 1 rash in 60% and diarrhea in 35%. There were 5 deaths during treatment in the G group v. one in the non-G group (p = 0.19). Only a projected 44% of pts will complete the 2-year course of G. With a median follow-up in this trial of 37 (range 13–64) months, 3-year Kaplan-Meier outcome estimates do not differ between the study and the historical cohorts. Local control without surgery is 80% v. 88% (p = 0.21), DM control is 86% v. 76% (p = 0.19), freedom from recurrence is 72% v. 71% (p = 0.79), and overall survival is 67% v. 68% (p = 0.63) respectively. Conclusions: The addition of G to our MACCRT regimen was difficult for pts to complete. It did not improve any measured outcome and was associated with increased toxicity when compared to historical controls. [Table: see text]

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18614-18614
Author(s):  
N. J. Tirgan ◽  
A. H. Hamrahian

18614 Background: Primary adrenocortical carcinoma (PAC) is a rare disease with a incidence of 1 per million. PAC’s are highly malignant tumors with guarded prognosis. Radical surgery is the treatment of choice. Methods: The pathology database and medical charts of these patients were retrospectively reviewed. Results: There were 14 females, 8 males, and 95% were caucasion. The mean age was 49.2 ± 11.8 years (females 51.6 years, males 45 years). The mean size of the tumor was 12.6 ± 5.1 cm (range of 3.6 to 25 cm). Thirteen patients (59.1%) presented with left and nine (40.9%) with right sided PAC. Seventy- two percent of the patients had abdominal, back, and/or flank pain. Forty five percent of patients had symptoms related to hypercortisolism and/or hyperandrogenism. Twelve patients (55%) had functional tumors (hypercortisolism 67%, hyperandrogenism 42%, and DHEA-S hypersecretion 42%) and ten were non-functional. Five percent of the tumors were classified as stage I, 33% were stage II, 38% were stage III, and 24% were stage IV. Twelve patients (55%) had distant metastases (liver 75%, lung 67%, retroperitoneum 33%, kidney 17%, contra-lateral adrenal gland 17%). All 22 patients had adrenalectomies (open 91%; laparoscopic 9%). The microscopic margin of resection were negative in 14 and positive in 6 patients. The information for 18 patients were evaluable for treatment. Eight patients received post-op therapy. Four patients received Mitotane (o,p’-DDD) alone (three died at 2, 29, and 213 months; and one is alive at 38 months after diagnosis). Three patients received both Mitotane and chemotherapy (two died at 3 and 43 months, one is alive at 140 months). One patient received only chemotherapy and died at 8 months. Ten patients received no post-op therapy. The estimated 5-year survival for the entire group was 48% (Kaplan-Meier survival estimate, 95% confidence interval). The estimated 5-year survival for stage III was 33%, and for stage IV was 30%. There were no deaths in patients with stage II group. The estimated 5-year survival for the treated group (8 patients) was 33% and 58% for the untreated group (10 patients). Conclusions: In PACs, surgery remains the main method of therapy. In our experience, Mitotane with or without chemotherapy did not improve survival. No significant financial relationships to disclose.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6061-6061
Author(s):  
Pau Guillen Sentis ◽  
Carmen Castillo Manzano ◽  
Beatriz Quirós ◽  
Francisca Morey Cortes ◽  
Sara Tous ◽  
...  

6061 Background: Treatment (ttm) of cancer patients (pts) was compromised during the first wave of COVID19 pandemic due to collapse of healthcare systems. Standard of care (SOC) for LA-HNSCC pts had to be adapted as operating rooms were temporarily unavailable, and to reduce risk of COVID19 exposure. The IMPACCT study evaluated the outcome of LA-HNSCC pts treated at the Catalan Institute of Oncology during the first semester of 2020 and compared it to a control cohort previously treated in the same institution. Methods: Retrospective single institution analysis of two consecutively-treated cohorts of newly-diagnosed HNSCC pts: from January to June of 2020 (CT20) and same period of 2018 and 2019 (CT18-19). Pt demographics and disease characteristics were obtained from our in-site prospective database. Ttm modifications from SOC as per COVID19-contingency protocol in CT20 for LA-HNSCC were collected. Chi-squared was used to compare variables and ttm response between cohorts. One-year recurrence-free survival (1yRFS) and overall survival (1yOS) of LA-HNSCC pts were estimated by Kaplan-Meier method and compared by Log-rank test. Results: A total of 306 pts were included: CT20=99; CT18-19=207. Baseline characteristics were balanced between cohorts (Table1). In pts treated with conservative ttm (non-surgical approach), persistence disease was higher in CT20 vs CT18-19 (26 vs. 10% p=0.02). Median follow-up of CT20 and CT18-19 was 6.8 months (IQR 5.1-7.9) and 12.3 (6.7-18.4), respectively. A trend towards lower 1yRFS and 1yOS was observed in CT20 vs CT18-19 (72 vs 83% p=0.06; 80 vs 84% p=0.07), respectively. Within CT20, 37 pts (37%) had one or more ttm modifications: switch from surgery to conservative ttm (n=13); altered radiotherapy fractionation (n=14); reduced cisplatin cumulative dose to 200mg/m2 (n=19); no adjuvant ttm (n=1). Pts who received modified ttm had no differences in 1yRFS vs those who did not (80 vs 66% p=0.31), but higher 1yOS was observed (97 vs 67% p<0.01). When stratified by stage, 1yOS difference remained significant in stage III/IVA (100 vs 61% p<0.01) but not in I/II (100 vs 77% p=0.28) or IVB (67 vs 50% p=0.54). Conclusions: COVID19 pandemic had a negative impact on ttm outcomes and survival in LA-HNSCC pts when compared to our historical cohort. Ttm modifications based on COVID19-contingency protocol did not compromise ttm efficacy in terms of RFS and was associated with better OS in Stage III/IVA.[Table: see text]


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7127-7127 ◽  
Author(s):  
J. P. Allerton ◽  
C. T. Hagenstad ◽  
R. T. Webb ◽  
G. B. Smith ◽  
R. Birch ◽  
...  

7127 Background: Abraxane (A) is a cremophor free, albumin-bound nanoparticle of paclitaxel (P) approved for the treatment of metastatic breast cancer. Belani et al. (JCO 21: 2933–2939, 2003) reported that P 100 mg/m2 days 1, 8 and 15 q 28 days with C AUC 6 on day 1 led to a 32% response rate in 132 patients (pts) with NSCLC. The median time to progression (TTP) was 35 weeks (wks) for stage IIIB and 29 wks for stage IV. Methods: This study was designed to determine if substituting A for P at an identical dose would lead to an improved response rate, TTP or decreased toxicity. Results: Fifty-six pts with stage IIIB/IV NSCLC previously untreated with chemotherapy were enrolled. The median age was 66 (range 37 - 83); 37 were male and median ECOG performance status was 1 (range 0–2). Thirteen pts were stage IIIB. Metastases included bone (17), liver (7), brain (2) and lymph nodes (16). Currently a total of 239 cycles of therapy have been administered with a median of 4 (range 1–8) cycles per pt. In 194 (81%) full dose A was administered on days 1, 8 and 15. The table below shows toxicities compared to P: Seven pts (13%) experienced grade (G) 1 neuropathy and 3 pts (5%) experienced G 2 neuropathy. Five pts were inevaluable for response due to removal from study after <2 cycles of treatment (2 died from progressive disease, 2 because of toxicity - thrombocytopenia and neutropenia - and 1 refused). Of 51 evaluable pts 1 (2%) had a complete response and 23 patients (45%) achieved a partial response. Four of 10 evaluable stage IIIB pts obtained a PR. Twenty-one pts were stable for at least 12 weeks of whom twenty remain stable at 12–29 weeks and one progressed at 23 weeks. A total of 13 pts have progressed and 3 pts have died. The Kaplan-Meier estimate of median TTP is 23 wks and maximum follow up is 34 wks. Conclusions: We conclude that combining A and C is tolerable and active in the treatment of newly-diagnosed NSCLC and antitumor activity compares favorably to that of P/C. Further studies are warranted in this population. [Table: see text] [Table: see text]


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8524-8524 ◽  
Author(s):  
John P. Fruehauf ◽  
Beverly Alger ◽  
Basmina Parmakhtiar ◽  
James G. Jakowatz ◽  
Claudette Bettis ◽  
...  

8524 Background: Metastatic melanoma lacks effective therapy. Pazopanib is a small-molecule inhibitor of VEGFR-1,2,3, PDGFR-B and c-KIT that has antiangiogenic activity in renal cell cancer as well as inhibition of melanoma tumor xenografts. We designed a phase II single arm, open label clinical trial evaluating pazopanib in combination with metronomic paclitaxel as first line therapy for subjects with unresectable stage III and stage IV melanoma. Methods: This protocol utilizes a Simon 2-stage Minimax design, with a planned interim analysis to confirm >3 responders to move to the second stage. To date, 20 eligible patients have been enrolled with 17 evaluable for response. All subjects were treatment naïve and received paclitaxel at 80mg/m2 weekly for three weeks in a 4 week cycle and pazopanib at 800mg as a continuous daily oral dose. The primary endpoint is 6 month progression free survival. Exploratory endpoints include biomarker analysis that may be associated with treatment outcomes (serum VEGF, soluble VEGF R2, serum HIF, serum TSP1 and BRAF mutation status). An additional exploratory endpoint includes the in vitro activity of pazopanib and paclitaxel on patient biopsy material co-cultured with vascular endothelial cells. RECIST criteria were used to define treatment response. Results: For the 17 evaluable patients treated to date the following results were seen: 1 CR, 6 PR’s, 8 SD’s and 2 PD’s. The overall RR (CR+PR) was 40%. Total disease control rate was 80% (PR+SD). The most common AEs/lab abnormalities were nausea (71%), hypertension (57%), fatigue (57%) and vomiting (43%). Grade 3-4 AEs included hypertension (28%), transaminitis (21%) and neutropenia (14%). One patient discontinued for grade 4 transaminitis which subsequently resolved completely. Dose reductions were required for pazopanib in 5 patients and for paclitaxel in one patient. Conclusions: Planned interim analysis of this phase II study demonstrated that pazopanib in combination with paclitaxel was well tolerated and resulted in a 40% response rate, indicating that this combination is of further interest. Accrual will continue to reach a goal of 60 patients.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5582-5582
Author(s):  
Jochen H. Lorch ◽  
Glenn Hanna ◽  
Wei Dai ◽  
Vijaya Thotakura ◽  
Vidya Nair ◽  
...  

5582 Background: HPV status is a major prognostic marker for survival in patients with OPC. We examined overall survival (OS) and progression free survival (PFS) in patients with OPC and known HPV status treated at Dana-Farber Cancer Institute with ST and CRT between 2002 and 2011. Methods: 280 patients with OPC and known HPV status were identified retrospectively and clinical information was recorded. Results: 174 patients were treated with CRT (124 HPV positive, 50 HPV negative) and 106 patients were treated with ST (77 HPV positive, 29 HPV negative). For all 280 patients, OS and PFS were significantly better for patients who were HPV positive compared to those who were HPV negative. 3 year OS was 89.1% for HPV positive (95% CI, 83.8-94.7) and 70.5% for HPV negative patients (95%CI, 59.9-83%, HR 0.37, p=0.0007). Among HPV positive patients treated with CRT, 13/124 had died at 3 years (OS 88.5%, 95%CI 81.7-95.9) while 13 deaths were recorded among 50 HPV negative patients (OS 72.2%, 95% CI 59.1-88.2, HR 0.38, p=0.011). PFS at 3 years was also significantly better for HPV positive versus HPV negative patients(81.7% vs 58.8%, HR 0.42, p=0.006). In the group treated with ST, outcomes were similar despite a higher rate of stage IV versus stage III disease compared to the group treated with CRT (100% stage IV in ST versus 77% stage IV and 23% stage III disease in CRT group). Three year OS was 89.7% for HPV positive and 68.2% in the HPV negative group (8/77 HPV pos vs 10/29 HPV neg, HR 0.33, p=0.015). PFS was borderline better for HPV positive patients (81% vs 61.7%, HR 0.48, p= 0.058). Conclusions: We present the DFCI experience treating OPC with ST and CRT for patients with known HPV status over one decade.OS and PFS were superior for HPV positive versus HPV negative patients. Outcomes were virtually identical for patients treated with CRT versus ST despite a higher rate of stage IV disease in the ST group. Outcomes for the HPV negative patients in particular were superior compared to the published literature.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 268-268
Author(s):  
Yehuda Ethan Deutsch ◽  
Danny Sleeman ◽  
Afonso Ribeiro ◽  
Dido Franceschi ◽  
Peter Joel Hosein ◽  
...  

268 Background: Cholangiocarcinoma is an uncommon malignancy. In addition, only 10-30% of patients are eligible for curative surgical resection due to advanced disease at diagnosis. The role of adjuvant therapy is not yet established. The objective of this analysis is to assess the outcome of patients with cholangiocarcinoma managed with surgery, chemotherapy, radiation, and/or chemo-radiation. Methods: From 1997 to 2007, patients with biliary cancer from the joint tumor registry database at UMH, SCCC, and JHS had their demographics, stage, pathology, treatment (surgical management, adjuvant and palliative therapy) and survival collected. A total of 800 patients with the diagnoses of biliary cancer were reviewed. The site of cancer was the bile duct in 351 patients, gallbladder in 173, and ampulla of vater in 239 patients. Results: Cholangiocarcinoma - adenocarcinoma of the bile duct – in 334 patients of the 351 with bile duct tumors were analyzed. The mean age at diagnosis was 65 (range 26-92) and 55% of patients were male. Stage at presentation was as follows: 22% of patients presented with stage I, 18% with stage II, 21% with stage III, 26% with stage IV, and 13% were unknown. Potentially curative surgical resection was performed in 45% of the patients. 24% received chemotherapy, 20% received radiation, and 14% received chemo-radiation in combination. The overall median survival (MS) of all patients was 13 months - 22, 16, 14, and 10 months for stages I, II, III, and IV respectively. Surgery provided an overall survival benefit for all stages (24 vs. 9 months, p<.001), including stage III (n=31/71; 20 vs. 10 months, p=.026) and stage IV (n=28/88; 23 vs. 6 months, p<.001). Chemotherapy offered a trend to survival benefit for patients with stage IV (13 vs. 6 months, p=.06) and combined stages III and IV (13 vs. 10 months, p=.07). Combination chemo-radiation had a significant survival benefit in stage IV (19 vs. 6 months, p=.022) and in combined stages III and IV (14 vs. 10 months, p=.026). Conclusions: Chemotherapy and chemo-radiation had a positive impact on survival in patients with late stage cholangiocarcinoma. Surgery improved survival in both early and advanced stages. The lack of data on performance status and organ function did not allow factoring these variables in the analysis.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 575-575
Author(s):  
Emmet Jordan ◽  
Amy Murphy ◽  
Seamus Coyle ◽  
Miriam O Connor ◽  
Paula Calvert ◽  
...  

575 Background: The incidence of CRC increases with age. Future numbers are projected to rise due to an ageing population. Little data exists on chemotherapy in those ≥80 years (yrs) with CRC, a subgroup rarely included in clinical trials. The purpose of this study was to evaluate chemotherapy use, feasibility and tolerability in patients ≥80 yrs with CRC in a single institution. Methods: CRC diagnosed in those ≥80 yrs in a single institution in Ireland , from 2004 -2009, was determined. Clinicopathological data collected included age, gender, morphology, stage, and treatment including surgery, radiation or chemotherapy. In those receiving chemotherapy tolerance was determined by dose delays, reductions and number of completed cycles. Results: 83 cases of CRC were identified; 80-89 yrs (n=78), 90-100 yrs (n=5). Median age was 84 yrs (range 80-102), 38/83 (45.8%) were female. 59 cases of colon and 24 cases of rectal cancer were seen. Stage at diagnosis included IV (n=18), III (n=21), II (n=38) and I (n=6). For stage IV disease 4/18 (22%) received chemotherapy. Median overall survival for those with stage IV disease who received chemotherapy was 317 days (range 64-487) versus 169 days (range 30-473) for supportive care. 3/21(14%) stage III patients received chemotherapy. Median survival for stage III disease who received chemotherapy was 1193 days (range 432-1640) compared to 641 days who did not (range 0-1640). All patients with stage IV disease received single agent (SA) treatment (capecitabine n=3, cetuximab n=1). Treatment of stage III disease included: XELOX n=1, 5Fluorouracil/Leucovorin n=1, capecitabine n=1). 3/6 (50%) had dose reductions (n=4) and delays (n=7) in treatment. 1 patient completed scheduled adjuvant treatment. 1 patient with metastatic disease received second and third line treatment (SA irinotecan, cetuximab). Data including performance status, co morbidity will be presented. Conclusions: The uptake of chemotherapy in this cohort is low. Although the rates of treatment modifications are high, those treated appear to benefit. Better clinical tools are needed to differentiate those older patients likely to benefit from systemic therapy and those better served by supportive measures alone.


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 441-441
Author(s):  
Mohammed Haseebuddin ◽  
Elizabeth Handorf ◽  
Joshua Jones ◽  
Alexander Kutikov ◽  
Nikhil Waingankar ◽  
...  

441 Background: There is currently no consensus regarding the use of systemic therapy (ST) for surgically-treated patients with invasive UTUC. Using a large national cancer registry, our objective was to assess temporal trends in utilization of ST for stage II-IV UTUC undergoing definitive resection. Methods: The National Cancer Database (NCDB) was queried for all patients surgically treated (nephroureterectomy, segmental resection) for stage II-IV UTUC from 1998-2012. Temporal trends in receipt of ST [neoadjuvant (NAT), adjuvant (AT), or unknown timing (UKT)] were assessed using chi square analyses. After exclusion of patients receiving NAT or UKT, adjusting for patient and clinicopathologic characteristics, multivariable logistic models were used to examine the association between clinicopathologic characteristics and receipt of ST within 9 months of resection. Kaplan Meier analyses and stratified log-rank tests were performed comparing overall survival (OS) between patients receiving ST < 9 months and those who did not. Results: Of 7,629 patients identified over the study period, 24.1% of patients surgically treated for stage II-IV UTUC received any ST (NAT: 1.44%, AT: 19.11%, UKT: 3.51%). Utilization of any ST significantly increased from 1998-2012 (20.2% vs. 28.7%, p < 0.0001). Following adjustment, patients of increased age (61-70 years: OR 0.62 [CI 0.42-0.91], 71+ years: OR 0.26 [CI 0.17-0.38]) were less likely to receive ST, and patients with high grade (OR 2.46 [CI 1.95-3.09]), Stage III (OR 4.75 [CI 3.89-5.79]), and Stage IV (OR 9.37 [CI 7.49-11.74]) disease were more likely to be treated with ST. When restricted to stage III-IV disease, receipt of ST < 9 months was significantly associated with improved OS after adjustment for age, grade, and charlson index (p < 0.002). Conclusions: In hospitals reporting to the NCDB, while utilization has significantly increased from 1998-2012, less than one third of patients surgically treated for stage II-IV UTUC receive ST. In addition to unmeasured characteristics (decline of renal function following surgery), the lack of explicit guidelines and prospective evidence may contribute to limited use of systemic treatment.


2020 ◽  
Author(s):  
Sarbani Ghosh-Laskar ◽  
Naveen Mummudi ◽  
Saurabha Kumar ◽  
Mukesh Chandre ◽  
Shagun Mishra ◽  
...  

ABSTRACTOBJECTIVEWe report the long term follow-up, toxicity, and outcomes of patients with localized squamous cell carcinoma of the esophagus (ESCC) who underwent definitive chemoradiotherapy (dCRT) at our institute.MATERIALS AND METHODSPatients diagnosed with carcinoma post cricoid, upper cervical and thoracic oesophagus and treated with dCRT treated between January 2000 and March 2012 were retrospectively analysed. Data was extracted from the hospital medical records and patient files. Patients deemed inoperable received upfront RT with or without concurrent chemotherapy and patients with borderline resectable and/or bulky disease received neoadjuvant chemotherapy followed by CRT or RT alone. Radiotherapy was delivered in two phases to a maximum dose of 63 Gy in daily fractions of 1.8 Gy using conventional or conformal techniques. Overall survival and progression free survival were defined from date of registration and were calculated by Kaplan-Meier method with comparisons between different subgroup performed using log rank test. All data were analyzed using SPSS Version 22.RESULTSThree hundred and fourteen patients with ESCC treated with dCRT were included in this analysis. Median age at presentation was 56 years and median Karnofsky Performance Status (KPS) at presentation was 70. Two-third of patients were treated with conformal technique alone or a combination of conventional and conformal technique. Median dose of radiation delivered was 60 Gy (range 30.6 Gy – 70 Gy). Neoadjuvant chemotherapy was administered in about 35% patients and 57% patients received concurrent chemotherapy. About 82% patients (77%) completed their planned treatment course; 10% patients required hospitalization during treatment due to complications and 7 patients did not complete treatment. Grade 1/2 dermatitis and mucositis was seen in 77% and 71% patients respectively. Grade 3 non-hematological and hematological toxicities were seen infrequently. Complete response at first follow up was observed in 56% of patients. At a median follow up of 56 months, 77 patients were alive with controlled disease. The 1-, 2- and 3-yr OS were 80%, 67% and 62% respectively. Median PFS was 28 months; 1-, 2- and 3-yr PFS were 66%, 52% and 46% respectively. A higher RT dose was found to be a significant predictor for OS and PFS on both uni- and multivariate analysis.CONCLUSIONOur study highlights that delivery of higher RT doses (≥63□Gy) is feasible in this patient group and that a higher RT dose was associated with significantly better PFS and OS.


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