Treatment of advanced squamous cell caricinomas of the head and neck with initial combination chemotheraphy prior to surgery and/or radiotheraphy: five-year survival data

1984 ◽  
Vol 98 (1) ◽  
pp. 75-82 ◽  
Author(s):  
H. J. Shaw ◽  
L. A. Price ◽  
Bridget T. Hill
Keyword(s):  
Complete Remission ◽  
Head And Neck ◽  
Survival Data ◽  
Residual Disease ◽  
Remission Rate ◽  
Histological Grade ◽  
Objective Response ◽  
Local Therapy ◽  
Chemotherapy Response ◽  
Response To Chemotherapy

AbstractOne hundred and thirty-nine patients with advanced head and neck cancer were treated with a combination of vincristine, bleomycin, methotrexate with a folinic acid rescue, 5-fluorouracil and hydrocortisone given over 24 hours, as initial therapy on days one and 14 prior to conventional local therapy on day 28. One hundred and thirty-six patients were assessed for chemotherapy response on day 28. Ninety-one patients (67 per cent) had an objective response and 45 (33 per cent) were classed as non-responders, although 13 had a minimal (20–30 per cent) response. The complete remission rate following local therapy was significantly greater in chemotherapy responders (76 per cent) than in non-responders (54 per cent) p<0.05. Toxicity was minimal, provided standard medical precautions were observed, and 87 patients (63 per cent) reported no side-effects. There was 100 per cent patient compliance. Sex or histological grade did not significantly influence response to chemotherapy. Oral cavity or nasopharyngeal tumours responded better than other sites (p<0.05). Patients under 49 were more likely to respond to chemotherapy than older patients (p<0.01). Survival data are available for a mean follow-up time of 48 months (range 12–78 months). Chemotherapy responders have a longermedian survival than non-responders, 33 versus 20 months (p<0.05). Patients who achieve a complete remission after local therapy live significantly longer than those with residual disease, median durations of survival being 52.4 and 7.8 months respectively (p<0.001). Actuarial analyses indicate that at five years 46 percent of patients in complete remission are alive, compared with only 9 per cent with residual disease. Since chemotherapy responders are significantly more likely to achieve a complete remission than non-responders (p<0.05), objective response to this schedule of chemotherapy is a good prognostic sign.

Cisplatin and fluorouracil chemotherapy does not yield long-term benefit in locally advanced head and neck cancer: results from a single institution.

1991 ◽  
Vol 9 (8) ◽  
pp. 1376-1384 ◽  
Author(s):  
E E Vokes ◽  
R Mick ◽  
E P Lester ◽  
W R Panje ◽  
R R Weichselbaum
Keyword(s):  
Head And Neck Cancer ◽  
Adjuvant Chemotherapy ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Neck Cancer ◽  
Survival Data ◽  
Locally Advanced ◽  
Local Therapy ◽  
Complete Response ◽  
Advanced Head

Fifty-one patients with locally advanced head and neck cancer were treated with three cycles of cisplatin at 100 mg/m2 followed by 5-day continuous infusion fluorouracil (5-FU) at 1,000 mg/m2/d as induction chemotherapy. Subsequent local therapy consisted of surgery for patients with resectable disease and/or radiotherapy. Three cycles of adjuvant chemotherapy were administered to patients with partial response (PR) or complete response (CR) to induction chemotherapy. Twenty-two patients (43%) had a clinical CR that was pathologically confirmed in 12 patients (24%), and 24 patients (47%) had a PR for an overall response rate of 90%. Local therapy included surgery in 24 patients (47%) and radiotherapy alone in 22 patients (43%). Adjuvant chemotherapy was administered to 32 patients (63%) frequently at great dose reduction. At a median follow-up of 90 months, the median survival is 22 months (95% confidence interval, 15 to 36 months), and the 5-year survival is 25%, with only five patients known to be alive and disease-free at this time. The median time to progression is 14 months, with 29 patients (57%) having documented progression of their head and neck cancer and eight (16%) having progression of a second neoplasm. Seven patients died of intervening medical events. This high incidence of second malignancies supports the continued investigation of chemoprevention for patients in CR. Despite the known high response rates achieved with cisplatin and 5-FU induction chemotherapy, the overall poor survival data reported here should lead to a thorough reexamination of the frequent administration of this regimen in the community.

scholarly journals Prognostic Value of MiR-21: An Updated Meta-Analysis in Head and Neck Squamous Cell Carcinoma (HNSCC)

2019 ◽  
Vol 8 (12) ◽  
pp. 2041 ◽  
Author(s):  
Irimie-Aghiorghiesei ◽  
Pop-Bica ◽  
Pintea ◽  
Braicu ◽  
Cojocneanu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Survival Data ◽  
Human Cancer ◽  
Meta Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
Potential Biomarker ◽  
Response To Chemotherapy

Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies with serious impact on patient quality of life due to a reduced rate of response to chemotherapy or radiation therapy. MiR-21 has been identified as one of the most common proto-oncogenes. It is hypothesized that upregulated miR-21 could serve as a potential biomarker for human cancer diagnosis. Considering the target genes identified for miR-21 in HNSCC, this transcript is an important player in several cellular processes that control carcinogenesis. The abnormal expression of miR-21 in this group of pathologies has been assessed in several publications, but given the heterogeneity of the published results, a meta-analysis and proper bioinformatics analysis of expression databases are needed to correctly establish the prognostic potential of this molecule. The present meta-analysis comprises the published survival data on HNSCC patients, reported as HR and 95% CI, in association with the expression levels of miR-21. Our investigation revealed that miR-21 could be used successfully as a prognostic biomarker in HNSCC patients, confirming its oncogenic potential. Specifically, the upregulation of miR-21 in these patients predicts a worse outcome in terms of survival rate.

Biomarkers predicting chemotherapy response in head and neck squamous cell carcinoma: a review

2015 ◽  
Vol 129 (11) ◽  
pp. 1046-1052 ◽  
Author(s):  
B Cosway ◽  
V Paleri ◽  
J Wilson
Keyword(s):  
Clinical Trial ◽  
Head And Neck ◽  
Evidence Base ◽  
Chemotherapeutic Agents ◽  
Head And Neck Cancers ◽  
Future Research ◽  
Chemotherapy Response ◽  
Oncological Treatment ◽  
Pubmed Database ◽  
Response To Chemotherapy

AbstractBackground:Biomarkers are increasingly being used in many cancers to select patients for oncological treatment paradigms based on their inherent genetic properties. However, in head and neck cancers, there are no personalised therapies available outside the context of a clinical trial. A number of studies suggest there are intrinsic tumour properties of head and neck cancers that affect their response to chemotherapeutic agents. This paper aimed to review their evidence base.Method:A narrative review was conducted following a search of the PubMed database.Results and conclusion:The review identified a number of biomarkers predicting response to chemotherapy in head and neck cancers. The paper discusses these in detail, and explores where future research could be directed in order to deliver personalised therapies for patients with head and neck cancers.

The AIM-HN Study: A pivotal study evaluating the efficacy of tipifarnib in patients with recurrent or metastatic head and neck squamous cell carcinoma with HRAS mutations.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS6087-TPS6087
Author(s):  
Robert I. Haddad ◽  
Douglas Adkins ◽  
Lisa F. Licitra ◽  
Justine Yang Bruce ◽  
Maura L. Gillison ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Survival Data ◽  
Objective Response ◽  
Neck Squamous Cell Carcinoma ◽  
Second Line ◽  
Pivotal Study ◽  
Line Setting

TPS6087 Background: Head and neck squamous cell carcinoma (HNSCC) accounts for more than 830,000 new cancer cases each year worldwide. The prognosis for recurrent and/or metastatic (R/M) HNSCC patients remains poor with an estimated median overall survival (mOS) of 7-15 months in the first line setting and 5-8 months in the second line setting and beyond. Approximately 4-8% of HNSCC tumors are driven by gain-of-function mutations in the HRAS (m HRAS) proto-oncogene. Tipifarnib is a potent and selective farnesyltransferase inhibitor that disrupts HRAS function by blocking required protein membrane localization, and subsequent cellular growth and survival. Data from a prior phase 2 study (RUN-HN; NCT02383927) of tipifarnib in R/M m HRAS HNSCC patients in the second line plus setting demonstrated encouraging efficacy, with an objective response rate (ORR) of 55% and mOS of 15.4 months for patients with mHRAS variant allele frequency (VAF) ≥ 20%, providing support for pursuing a pivotal trial in this patient population. Methods: AIM-HN (NCT03719690) is a global, open-label single-arm pivotal study evaluating the efficacy and tolerability of tipifarnib in second line plus R/M m HRAS HNSCC patients. The primary objective is to determine the ORR in patients with a m HRAS VAF ≥ 20% (High VAF population), as assessed using RECIST v1.1 by Independent Review Facility. Key secondary objectives include the ORR for patients of all VAF levels, and the duration of responses for both VAF≥ 20% and all VAF levels. Key inclusion criteria include: histologically confirmed head and neck cancer of squamous histology not amenable to local therapy with curative intent; known tumor missense HRAS mutation (with VAF determined and available) detected by Next Generation Sequencing; ECOG performance status of 0-1; measurable disease by RECIST v1.1; and adequate organ function. Key exclusion criteria include: salivary gland, thyroid, (primary) cutaneous squamous or non-squamous histologies; intolerable Grade 2 or ≥ Grade 3 neuropathy or unstable neurological symptoms within 4 weeks of Cycle 1 Day 1; or active, uncontrolled infections requiring systemic therapy. Tipifarnib is administered at a dose of 600 mg, orally with a meal twice a day for 7 days in alternating weeks (Days 1-7 and 15-21) of 28-day cycles until discontinuation criteria are met. All patients are being followed for safety through the End of Treatment visit, roughly 30 days after treatment discontinuation or immediately before the administration of another anticancer treatment, whichever occurs first. Upon therapy discontinuation, all patients are being followed approximately every 12 weeks for survival status, and the use of subsequent therapy. The IDMB last reviewed data in October 2020 and recommended the trial continue as planned. AIM-HN is continuing to enroll patients globally. Ho et al, JCO, accepted. Clinical trial information: NCT03719690.

Effect of anti-CD19 BiTE blinatumomab on complete remission rate and overall survival in adult patients with relapsed/refractory B-precursor ALL.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6500-6500 ◽  
Author(s):  
Max Topp ◽  
Nicola Goekbuget ◽  
Gerhard Zugmaier ◽  
Andreas Viardot ◽  
Matthias Stelljes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Residual Disease ◽  
Remission Rate ◽  
Day Treatment ◽  
Adult Patients ◽  
Complete Remission Rate ◽  
Target Cells ◽  
Partial Recovery ◽  
Final Dose

6500^ Background: Blinatumomab is a bispecific T-cell engaging (BiTE) antibody that directs cytotoxic T-cells to CD19 expressing target cells. Methods: In adult patients with relapsed/refractory B-precursor ALL, a phase II dose ranging trial is being conducted to evaluate efficacy and safety of blinatumomab. The primary endpoint is the rate of hematological complete remission (CR) or CR with partial hematological recovery (CRh*) within 2 cycles of blinatumomab treatment. Blinatumomab is administered by continuous intravenous infusion for 28-days followed by a 14-day treatment-free interval. Responding patients can receive 3 additional cycles of treatment or proceed to bone marrow transplantation. Three dose levels were explored as shown in the table. Results: In total 36 patients have been enrolled, 25 are currently evaluable. Seventeen out of 25 treated patients (68%) reached a hematological CR/CRh* and a minimal residual disease (MRD) response (MRD level <10-4) within the first 2 cycles. Five out of 17 responders (29%) showed a CRh* due to partial recovery of platelets. For the first 18 patients, response duration is 7.1 months and the median follow-up time for overall survival (OS) is 9.7 months (median not reached). Six cases of relapses have been recorded of which 3 were CD19+, and 3 CD19-. As final dose 5 µg/m²/day in week 1 and 15 µg/m²/day for the remaining treatment (cohort 2a and 3) was selected. In these cohorts (n=12), the most common treatment emergent adverse events (TEAEs, all grade 1-2) were pyrexia (67%), headache (33%) and tremor (33%). TEAEs of grade ≥3 (7 in 5 patients, no grade 4), irrespective of relationship, were infections, confusion, epilepsy, hypertension and thrombocytopenia. Conclusions: The final dose was well-tolerated and produced an exceptionally high complete remission rate. A global phase 2 study to confirm these data is underway. [Table: see text]

Importance of primary site in assessing chemotherapy response and 7-year survival data in advanced squamous-cell carcinomas of the head and neck treated with initial combination chemotherapy without cisplatin.

1986 ◽  
Vol 4 (9) ◽  
pp. 1340-1347 ◽  
Author(s):  
B T Hill ◽  
L A Price ◽  
K MacRae
Keyword(s):  
Oral Cavity ◽  
Head And Neck ◽  
Median Survival ◽  
Squamous Cell ◽  
Response Rate ◽  
Local Therapy ◽  
Squamous Cell Carcinomas ◽  
Chemotherapy Response ◽  
Tumor Site ◽  
Nasopharyngeal Tumors

Two hundred eight patients with advanced head and neck squamous-cell carcinomas were treated between 1975 and 1982 with schedule A chemotherapy containing vincristine, bleomycin, methotrexate, 5-fluorouracil, and hydrocortisone administered over 24 hours followed by a folinic acid rescue. Chemotherapy was administered as initial treatment on days 1 and 14 before "curative" local therapy. Toxicity was minimal and patient compliance was 100%. Chemotherapy response was assessed on day 28 in 200 patients: 132 (66%) had an objective response and 68 (34%) were judged to be nonresponders. The complete remission (CR) rate following local therapy was significantly greater in chemotherapy responders (78%) than nonresponders (49%) (P less than .001). Overall median survival figures were 32 months for all patients, 37 months for all chemotherapy responders, and 69 months for all patients achieving CR. Analysis by tumor site showed that oral cavity or nasopharyngeal tumors responded well to initial chemotherapy (P less than .05 and P less than .01) compared with all other sites. This high response rate was not necessarily associated with increased survival, since the median survival of chemotherapy responders for oral cavity lesions was only 22 months, although in nasopharyngeal tumors, median survival figures were 64 months. Furthermore, the longest median survival duration of 69 months was observed in patients with laryngeal tumors, although these had a lower response rate (61%) to initial chemotherapy. Therefore, response to initial chemotherapy is not automatically a favorable prognostic sign. Survival figures appear markedly influenced by tumor site.

scholarly journals Circulating Biomarkers for Prediction of Objective Response to Chemotherapy in Pancreatic Cancer Patients

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 93 ◽  
Author(s):  
Fleur van der Sijde ◽  
Eveline Vietsch ◽  
Dana Mustafa ◽  
Marc Besselink ◽  
Bas Groot Koerkamp ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Systemic Chemotherapy ◽  
Therapeutic Option ◽  
Objective Response ◽  
Survival Rates ◽  
Best Supportive Care ◽  
Chemotherapy Response ◽  
Circulating Biomarkers ◽  
Response To Chemotherapy ◽  
Palliative Systemic Chemotherapy

Pancreatic cancer is a lethal disease with increasing incidence. Most patients present with advanced disease, for which palliative systemic chemotherapy is the only therapeutic option. Despite improved median survival rates with FOLFIRINOX or gemcitabine chemotherapy compared to the best supportive care, many individual patients may not benefit from chemotherapy. Biomarkers are needed to predict who will benefit from chemotherapy and to monitor a patient’s response to chemotherapy. This review summarizes current research and future perspectives on circulating biomarkers for systemic chemotherapy response.

scholarly journals Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adults

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 38-47 ◽  
Author(s):  
D Hoelzer ◽  
E Thiel ◽  
H Loffler ◽  
H Bodenstein ◽  
L Plaumann ◽  
...  
Keyword(s):  
Complete Remission ◽  
Remission Rate ◽  
Lymphoblastic Leukemia ◽  
Early Response ◽  
Response To Therapy ◽  
Delayed Response ◽  
Childhood All ◽  
Remission Duration ◽  
Response To Chemotherapy ◽  
Adverse Influence

Abstract One hundred seventy adult patients with acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia (AUL) were entered into a prospective multicenter therapy trial at 25 hospitals. The aim of the trial was to improve remission duration by using a modified form of an intensified induction regimen that was successful in childhood ALL, to define immunologic subtypes of ALL by use of cell-surface markers, and to extract other possible prognostic factors. The overall complete remission rate was 77.8%. The median overall survival time was 26 months, being 4 months for nonresponders and 32 months for responders. The median remission duration for the 126 patients with complete remission was 20 months. Prognostically favorable factors for remission duration were response to chemotherapy within 4 weeks, age less than 35 years, a low initial leukocyte count, and the immunologic subtypes c- ALL with early response to therapy and T-ALL, where 61% and 58%, respectively, are still in complete remission at 3 years. An adverse influence on remission duration was observed for the subtype null-ALL, with a median survival of 13 months, and for patients with a delayed response to induction therapy, independent of phenotype.

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