Aspirin may stop deafness caused by chemotherapy

Author: staff

Aspirin could save the hearing of cancer patients receiving chemotherapy, scientists in Cardiff hope.

A trial will be launched at the city’s Velindre Hospital to see if high doses of the drug can prevent permanent loss.

Conditions ranging from tinnitus to deafness are a common side effect for patients given the chemotherapy drug cisplatin.

The trial, called Coast, has recruited 88 adults prescribed cisplatin in Cardiff and other UK hospitals.

It is used to treat testicular cancer, germ cell cancer, head and neck cancer, bladder cancer, cervical cancer, non-small cell lung cancer and some types of children’s cancer.

‘Shock it was cancer’
Father-of-four Andrew Millington, 66, was given cisplatin after a tumour was found at the base of his tongue.

“I had a persistent sore throat and earache, and I went to see my GP last spring,” he said.

“I was referred to a consultant and had an MRI scan. It was a shock to be told it was cancer but… it was generally curable, which was such a relief to hear. I was offered cisplatin and, after hearing about the possible side effects, I was more than happy to take part in the Coast trial.”

Around 18,500 cancer patients receive cisplatin every year and around half suffer some form of permanent hearing loss.

Ahead of the trial’s launch on Thursday, professor Emma King, chief investigator and Cancer Research UK surgeon at the University of Southampton, said: “Aspirin can have serious side effects, including internal bleeding, so it’s important to stress that aspirin is not suitable for all cancer patients.

“To help prevent these problems we’ll be giving patients specially coated aspirin tablets, that only release the drug once it reaches the small intestine, and also using another drug that reduces digestive juices, to prevent bleeding in the stomach.

“If this trial is successful, then a larger trial will follow within two years that could potentially see aspirin become a routine part of cisplatin treatment for many thousands of cancer patients.”

Experimental EGFR inhibitor added nothing but rash

Author: Neil Osterweil, Oncology Report Digital Network

The addition of the experimental targeted agent zalutumumab to primary curative chemoradiation for head and neck cancers did not improve locoregional control, disease-specific survival, or overall survival at 3 years of follow-up.

The only thing that zalutumumab added to therapy was a skin rash in the large majority of patients who received it, reported Dr. Jens Overgaard, of the department of experimental clinical oncology at Aarhus University, Denmark.

Response to zalutumumab, a monoclonal antibody targeted to the epidermal growth factor receptor (EGFR), was not related to tumor human papillomavirus 16 (HPV/p16) status or to chemoradiotherapy, Dr. Overgaard reported at the Multidisciplinary Head and Neck Cancer Symposium.

The results of the DAHANCA 19 trial echo those of the RTOG (Radiation Oncology Therapy Group) trial 0522, which found no benefit from the addition of the EGFR inhibitor cetuximab (Erbitux) to accelerated cisplatin-based chemoradiotherapy, said Dr. Paul Harari, an invited discussant from the University of Wisconsin, Madison.

“Where I think we have a lot of unanswered questions is acknowledging how little we actually understand about EGFR biology, despite now 40 years of progressive knowledge,” Dr. Harari said.

“We’re now seeing very clearly in molecular and clinical correlate studies that the more we suppress the EGFR, the more we see collateral overexpression of additional RTKs [receptor tyrosine kinases], including members of the HER family, such as HER-3, that enable an escape mechanism for tumors that become resistant to EGFR inhibition,” he said.

Dr. Overgaard and his colleagues in the Danish Head and Neck Cancer Group conducted an open-label, phase III trial in which 619 patients with nonmetastatic squamous cell carcinomas of the larynx, oropharynx, hypopharynx, or oral cavity were randomly assigned to received 66-68 Gy of accelerated radiotherapy with or without zalutumumab 8 mg/kg weekly, with the first dose given a week before the start of radiation. The radiation was given concomitantly with the radiosensitizer nimorazole and, in patients with involved lymph nodes, cisplatin.

A total of 301 patients who received zalutumumab and 307 controls were included in the final intention-to-treat analysis.

At 3-year follow-up, there were no significant differences in either the primary endpoint of locoregional control (76% in zalutumumab-treated patients and 77% of controls) or in the secondary endpoints of disease-specific survival (82% and 85%, respectively) or overall survival (72% and 79%), Dr. Overgaard reported at the symposium, cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.

Overall, patients who were positive for the HPV/p16 biomarker fared better than p16-negative patients, with an odds ratio for the probability of local control in negative patients of 0.52 (95% confidence interval, 0.36-0.73; P value not reported).

However, regardless of HPV 16 status, the addition of zalutumumab made no difference in the primary endpoint.

In a proportional hazard analysis, factors significantly associated with worse outcomes included worse World Health Organization performance status, higher disease stage, nodal involvement, and HPV/p16 negative status.

Although zalutumumab was generally well tolerated, 94% of patients who received it developed a rash, and of this group, 29% had grade 3 or 4 rash. In all, 11% of patients assigned to zalutumumab had to stop the drug because of rash.

The trial was sponsored by the Danish Head and Neck Cancer Group. Dr. Overgaard reported having no financial disclosures. Dr. Harari has received research funding from Amgen.

March, 2014|Oral Cancer News|

Chemoradiation offered better survival than accelerated radiation in head and neck squamous cell carcinomas

Author: Neil Osterweil, Oncology Report Digital Network

Concurrent chemoradiation offered better overall survival and disease-free survival than accelerated radiotherapy in patients with moderately advanced squamous cell carcinomas of the head and neck, investigators reported at the Multidisciplinary Head and Neck Symposium.

Actuarial rates of 2-year overall survival and disease-free survival in patients treated with concurrent chemoradiation (CCR) were significantly better than for patients treated with accelerated radiotherapy alone, reported Dr. Krzysztof Skladowski of the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Gliwice, Poland.

“CCR with conventional 7 weeks of fractionation and at least two courses of high-dose cisplatin is more effective than 6 weeks of accelerated radiotherapy alone,” he said.

Even if patients can tolerate only a single course of cisplatin, CCR is still superior to accelerated radiation, he added.

The findings suggest that accelerated radiation protocols should be reserved for patients with more favorable prognosis, such as those with stage T2 disease with limited nodal involvement, and those who are positive for the human papillomavirus (HPV) p16 protein, Dr. Skladowski said at the symposium cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.

The findings are “concordant with data that has been emerging now over approximately 10-14 years of the value of concurrent chemoradiation in head and neck cancer for a substantial cohort of patients over radiation alone,” said Dr. Paul Harari of the University of Wisconsin, Madison, and the invited discussant.

Although a previous meta-analysis (Lancet 2006; 368:843-54) suggested that accelerated or hyperfractionated radiotherapy was associated with a 3.4% advantage in overall survival, compared with conventional radiotherapy over 5 years, there have been no randomized studies comparing accelerated radiotherapy protocols with concurrent chemoradiation in this population, Dr. Skladowski said.

He and colleagues compared the two modalities in 101 patients with moderately advanced cancers of the oropharynx (46 patients), hypopharynx (19), and larynx (36).

They defined moderately advanced cancers as stage T2N1-2, T3N0-2, or T4AN0-2 if the involved nodes are not larger than 3 cm in diameter. Patients with oropharyngeal cancers were tested for expression of the human papillomavirus (HPV) p16 protein.

Patients were randomly assigned to receive either concurrent chemoradiation with intensity-modulated radiation therapy–delivered doses of 66-70 Gy divided into 33-35 daily fractions over 45-49 days plus cisplatin 100 mg/m2, delivered on days 1, 2 and 43, or to accelerated radiotherapy delivered via intensity-modulated radiation therapy in 1.8 Gy fractions 7 days/week to a total dose of 66.2-72 Gy.

Five patients in the CCR arm received only one dose of cisplatin, 30 received two doses, and 13 received the planned three doses.

At a median follow-up of 30 months, actuarial rates of 2-year overall survival of patients treated with CCR were 81%, compared with 62% for patients treated with accelerated radiation (P = .02). Disease-free survival rates were 75% and 60%, respectively (P = .05).

Acute adverse events were similar, with approximately 80% of patients in each treatment arm experiencing confluent mucositis, and about 10% having grade 3 dysphagia. There were no grade 4 toxicities.

The majority of treatment failures in each group were local, occurring in 21 of 52 patients treated with radiation alone, and in 11 of 49 patients treated with CCR (P = .03).

Significantly more deaths occurred in the radiation alone arm: 20 vs. 9 (P =.02).

The 2-year disease-free survival rate among patients in the CCR arm was dose dependent, at 60% of patients who received one course of cisplatin, 77% of those who received two courses, and 79% for those who received all three.

At the time of the analysis, all patients with oropharyngeal cancer who were positive for HPV p16 (five treated with accelerated radiation and six with CCR) were alive with no treatment failure. The overall survival rate for HPV-positive patients was 60% in the radiation only arm, and 80% in the CCR arm.

The study was supported by the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology. Dr. Skladowski reported having no financial disclosures. Dr. Harari has received research funding from Amgen.

March, 2014|Oral Cancer News|

PTEN loss, PIK3CA mutation predicted resistance to cetuximab in HNSCC

June 2, 2013


CHICAGO — PTEN loss or PIK3CA mutation predicted resistance to treatment with cisplatin plus cetuximab in a cohort of patients with head and neck squamous cell carcinoma, according to phase 3 study results presented at the ASCO Annual Meeting.

“Cetuximab is the only targeted therapy in use in head and neck cancer, and although it prolongs survival, the effects are modest. For patients who receive [cetuximab] in the setting of metastatic or recurrent disease, median survival remains less than 1 year,” Barbara Burtness, MD, a medical oncologist at Fox Chase Cancer Center who specializes in head and neck cancers and a HemOnc Today Editorial Board member, said in an interview. “In colon cancer, patients are tested for KRAS mutations to detect patients with upfront resistance to cetuximab, but KRAS mutation is rare in head and neck cancer, and we haven’t had a biomarker to separate the sensitive from resistant patients.”

Burtness and colleagues compared cisplatin plus placebo vs. cisplatin plus cetuximab (Erbitux, Eli Lilly) in 117 patients. The researchers also assessed PIK3CA mutations and loss of PTEN expression in the cohort.

Results indicated that 34% of tumors studied had a loss of PTEN expression and 4% had PIK3CA mutations in the three hotspots studied.

Researchers did not observe any statistically significant differences in OS, PFS or overall response rates.

However, among patients with PIK3CA and PTEN expression, median PFS was 4.2 months for those assigned to cetuximab vs. 2.9 months for those assigned to placebo (adjusted P value=.07). Among patients with PIK3CA mutations but without PTEN expression, median survival was 4.6 months for those assigned to cetuximab and 3.5 months for those assigned to placebo.

“This study was limited by the small size of the original clinical trial, as well as by the fact that specimens were not available for all the patients, so the results are of borderline statistical significance,” Burtness said. “But if these data are corroborated in larger cohorts of cetuximab-treated patients, they would suggest that PTEN loss together with PIK3CA mutation could serve as a signature to identify patients who will not benefit from cetuximab therapy as it is currently given. The advent of PIK3 inhibitors could give us a new treatment strategy for these patients, potentially in combination with cetuximab.”


* This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.


June, 2013|Oral Cancer News|

Are combination therapies effective for advanced SCCHN?

Author: DrBicuspid Staff

In a recent study, researchers from the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center examined whether the addition of multiple drugs to radiation therapy is superior to the current standard of care therapy with one drug and radiation for locally advanced squamous cell carcinoma of the head and neck (SCCHN).

Their data, published in the Journal of Clinical Oncology, suggests that it does not (March 4, 2013). Standard therapy for SCCHN is a combination of the drug cisplatin and radiotherapy.

This clinical trial compared this combination to the combination with the addition of a small-molecule inhibitor of the epidermal growth factor receptor (EGFR) erlotinib. For the study, 204 patients with locally advanced SCCHN were recruited between December 2006 and October 2011. Participants were assigned to receive either cisplatin and radiotherapy or the same chemoradiotherapy with erlotinab.

EGFR is a therapeutic target for this type of cancer, and at least one other EGFR is approved for multiple uses in treating head and neck cancer, including in combination with radiation. To date, no data have been published on the use of EGFR inhibitors in combination with chemotherapy and radiation.

The goal of the current study was to determine if adding EGRF inhibition improved efficacy when combined with standard of care radiation. Unfortunately, the researchers found that the addition of EGRF did not improve clinical response rate or progression-free survival.

“There has been great enthusiasm and some confusion about the combinations of chemotherapy and biologic therapy such as EGFR inhibitors in conjunction with radiation in the treatment of squamous cell carcinomas of the head and neck,” stated lead author Neil Hayes, MD, MPH, from UNC Lineberger Comprehensive Cancer Center, in a press release. “For the moment, the data are clearly showing no added benefit.”

Future investigations will rely more on patients selected by the molecular tumor characteristics, he added.

Other institutions participating in the study were the University of Washington, Fred Hutchinson Cancer Research Center, Multicare Health Systems, University of New Mexico, Medical University of South Carolina, University of Miami, Coastal Carolina Radiation Oncology, and the University of Tennessee. Funding for the study was provided to the University of Washington by Genentech and Astellas Pharma Global Development.

March, 2013|Oral Cancer News|

Targeted Drugs No Help in Head and Neck Cancer

Author: Charles Bankhead, Staff Writer, MedPage Today
Date: March 05, 2013

The addition of targeted agents to standard chemotherapy failed to improve efficacy in two different trials of advanced head and neck cancer.

In one trial, patients given gefitinib (Iressa) in addition to docetaxel lived about a month longer than those who received docetaxel plus placebo. In the other trial, adding erlotinib (Tarceva) to cisplatin-based chemoradiation did not improve response rate or progression-free survival.

However, neither regimen was associated with increased toxicity compared with standard chemotherapy, investigators reported online in the Journal of Clinical Oncology.

Noting the lack of useful biomarkers to guide the use of targeted agents, the authors of an accompanying editorial said that experience to date suggests current strategies amount to “skimming the surface of a problem that is exceedingly complex.”

“It is unlikely that genomic sequencing alone will represent a panacea to the therapeutic challenges in squamous cell carcinoma of the head and neck,” said Aaron R. Hansen, MBBS, and Lillian L. Siu, MD, of Princess Margaret Cancer Center in Toronto. “Comprehensive characterization that encompasses a broader omics-based molecular evaluation, as well as immune function assessments, is urgently needed.”

The rationale for the gefitinib and erlotinib trials came from evidence that the drugs targeting epidermal growth factor receptors (EGFR) have synergism with conventional chemotherapeutic agents, have radiosensitizing properties, and have demonstrated modest activity as monotherapy in some clinical studies.

Cetuximab (Erbitux), another EGFR inhibitor, has been approved for use with radiation therapy or as monotherapy in selected patients with head and neck cancer.


Preliminary studies of the docetaxel-erlotinib combination showed considerable toxicity that required dose reductions. As a result, the investigators chose to evaluate gefitinib in combination with docetaxel.

“Our hypothesis was that the addition of gefitinib to docetaxel will be synergistic and improve outcomes of previously treated and/or compromised performance status patients with recurrent or metastatic squamous cell carcinoma of the head and neck,” Athanassios Argiris, MD, of the University of Texas Health Science Center at San Antonio, and co-authors wrote.

Eligible patients had recurrent or metastatic disease and Eastern Cooperative Oncology Group (ECOG) performance status 2 or ECOG 0 to 2 and previous exposure to chemotherapy. All patients received weekly docetaxel and were randomized to gefitinib or placebo.

Treatment continued until disease progression, and the primary endpoint was overall survival.

The phase III trial had a patient-accrual goal of 330, but enrollment ended after 270 patients when an interim analysis suggested efforts to demonstrate improvement in the primary endpoint would prove futile.

The results showed a median overall survival of 6 months in the docetaxel-placebo arm and 7.3 months with the docetaxel-gefitinib regimen. An unplanned analysis suggested that patients younger than 65 benefited from gefitinib (7.6 versus 5.2 months median overall survival, P=0.04).

Grade 3/4 toxicity occurred in a similar proportion of patients in both treatment arms, with the exception of diarrhea, which was more common with gefitinib.


The erlotinib trial involved 204 patients with locally advanced squamous cell carcinoma of the head and neck. All patients received cisplatin-based chemoradiation and were randomized to the EGFR inhibitor or no further therapy.

The primary endpoint was complete response rate, and progression-free survival (PFS) was the secondary endpoint, as reported by Renato G. Martins, MD, of the University of Washington in Seattle, and colleagues.

The results showed a complete response rate of 40% without chemoradiation and 52% with chemoradiation plus erlotinib, a difference that did not achieve statistical significance (P=0.08). After a median follow-up of 26 months, PFS also did not differ significantly between the two treatment arms (HR 0.9, P=0.71).

Investigators prospectively evaluated p16 status in 90 patients. A positive result was defined as “strong, diffuse nuclear and cytoplasmic staining in ≥70% of tumor cells.” Patients with p16-positive tumors had significant improvement in the hazard for progression when they received erlotinib (HR 0.39, P=0.04).

Martins and colleagues also evaluated the relationship between development of rash and PFS in patients who received erlotinib. The analysis revealed rash as a significant predictor of improved PFS (HR 0.41 versus erlotinib-treated patients without rash, P=0.03).

“Despite preclinical data suggesting that erlotinib could be synergistic with both chemotherapy and radiotherapy, erlotinib previously failed to improve outcome in metastatic non-small cell lung cancer,” Martins and colleagues noted in their discussion. “Here, erlotinib failed to improve the outcome of locally advanced squamous cell carcinoma of the head and neck when combined with cisplatin-radiotherapy.”

Although disappointing, the results do not represent the end of the line for investigation of targeted agents in head and neck cancer, Ellie Maghami, MD, of City of Hope in Duarte, Calif., told MedPage Today. Echoing the sentiments of Hansen and Liu, Maghami said the true potential of targeted agents in head and neck cancer will not be determined in the absence of accurate biomarkers to guide patient selection.

The gefitinib study was supported by AstraZeneca. The erlotinib study was supported by Genentech.

Argiris disclosed a relationship with AstraZeneca. Co-authors disclosed relationships with AstraZeneca, Boehringer Ingelheim, Genentech, and sanofi-aventis.

Martins disclosed relationships with Genentech and OSI Pharmaceuticals. Co-authors disclosed relationships with XCENDA Amerisource Bergen Consulting Services, Genentech, Intuitive Surgical, and OSI Pharmaceuticals.

Siu disclosed relatinships with Roche, Pfizer, Bristol-Myers Squibb, and Boehringer Ingelheim.

Primary source: Journal of Clinical Oncology
Source reference:
Argiris A, et al “Phase III randomized, placebo-controlled trial of docetaxel with or without gefitinib in recurrent or metastatic head and neck cancer: An Eastern Cooperative Oncology Group trial” J Clin Oncol 2013; DOI: 10.1200/JCO.2012.45.4272.

Additional source: Journal of Clinical Oncology
Source reference:
Martins RG, et al “Cisplatin and radiotherapy with or withoout erlotinib in locally advanced squamous cell carcinoma of the head and neck: A randomized phase II trial” J Clin Oncol 2013; DOI: 10.1200/JCO.2012.46.3299.

Additional source: Journal of Clinical Oncology
Source reference:
Hansen AR, Siu LL “Epidermal growth factor receptor targeting in head and neck cancer: Have we been just skimming the surface?” J Clin Oncol 2013; DOI: 10.1200/JCO.2012.47.9220.


 * This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

March, 2013|Oral Cancer News|

Erbitux add-on falls short in esophageal cancer

Author: Charles Bankhead, Staff Writer, MedPage Today

The addition of a targeted agent to definitive chemoradiation failed to improve survival in an unselected population with esophageal cancer, a randomized trial showed. In fact, patients who received cetuximab (Erbitux) with chemoradiation had significantly worse overall survival (OS) reflected in a 50% increase in the hazard versus chemoradiation alone, reported Thomas Crosby, MD, of Velindre Hospital in Cardiff, Wales, and colleagues.

Investigators could not find any subgroup of patients who benefited from cetuximab, they said in a presentation at the Gastrointestinal Cancers Symposium.

“The addition of cetuximab cannot be recommended to standard definitive chemoradiotherapy in the treatment of unselected patients with esophageal cancer,” Crosby said.

“The use of high-quality definitive chemoradiotherapy in the treatment of localized, poor-prognosis esophageal cancer was associated with excellent survival compared with previous radiotherapy and surgical series,” he added.

Randomized trials have shown that definitive (or primary) chemoradiation improves survival in localized esophageal cancer compared with a single treatment modality. In England, definitive chemoradiation has been used primarily for patients with localized disease that is unsuitable for surgery, Crosby said.

Add-on therapy with cetuximab has improved outcomes in other cancers, notably head and neck cancer and colorectal cancer. The findings provided a rationale for evaluating the addition of cetuximab to primary radiation therapy for localized esophageal cancer.

Crosby presented results of a randomized trial wherein patients with localized (stage I-III) esophageal cancer (less than 10 cm). Patients were excluded if they had celiac lymph-node involvement.

The patients received cisplatin-capecitabine (Xeloda) chemotherapy with or without cetuximab. After 6 weeks of chemotherapy, patients underwent definitive conformal radiation therapy at a total dose of 50 Gy in 25 fractions.

The trial had two stages. The first stage had a primary endpoint of treatment failure-free survival (TFFS), defined as alive at 6 months with no residual cancer in biopsy specimens and no evidence of disease progression outside the radiation therapy field. Secondary endpoints were toxicity, quality of life, overall survival (OS), and feasibility of recruitment. The first stage of the trial had an accrual target of 180 patients.

The trial’s second stage had a primary endpoint of OS and accrual to 420 patients.

However, the trial never reached second stage, but ended after a planned stage one analysis convinced the independent review committee that continued accrual to meet the primary endpoint would be futile.

Treatment and follow-up continued with enrolled patients, and the final analysis included 258 patients who had completed the 6-month assessment of disease status.

Crosby reported that patients randomized to conventional chemoradiation without cetuximab had a TFFS of 77% whereas the cetuximab group had a TFFS of 66%. All survival outcomes favored omission of cetuximab:

Median OS: 25.4 months versus 22.1 months
2-year survival: 56% versus 43.1%
Median progression-free survival: 19.4 months versus 15.9 months
The analysis showed a marked difference in median OS between patients who met the TFFS goal at 6 months and those who did not: 26.7 months versus 8.3 months.

Comparison of OS in the two arms yielded hazard ratio of 1.53 for the cetuximab arm versus chemoradiation only (P=0.035).

In addition to the inferior outcomes with cetuximab, addition of the targeted agent added to the toxicity burden. The cetuximab arm had an 81.4% incidence of grade 3 to 5 toxicity compared with 72.9% without cetuximab.

Patients who received cetuximab in addition to chemoradiation had significantly more grade 3 to 5 dermatologic toxicity (21.7% versus 3.9%, P<0.001) and metabolic/biochemical toxicity (24.0% versus 10.9%, P=0.005).

Additionally, the analysis revealed a trend toward more cardiac adverse events in the cetuximab arm (6.2% versus 1.6%, P=0.053).

The addition of cetuximab also adversely affected adherence to the treatment protocol. Patients in the cetuximab arm were significantly less likely to receive full doses of cisplatin (76.7% versus 89.9%, P=0.005), capecitabine (69.0% versus 85.3%, P=0.002), and radiation therapy (75.2% versus 86.0%, P=0.027).

Additionally, almost a third of patients did not receive the prescribed dose of cetuximab.

“Future strategies to improve the outcome of definitive chemoradiotherapy in esophageal cancer must focus on developing evidence-based biomarkers to select treatments and incorporating newer radiotherapy technologies and targeted systemic treatment to safely intensify treatment, including a higher radiotherapy dose,” Crosby said.

January, 2013|Oral Cancer News|

Ten year results of landmark neck cancer trial published

Author: Gabriel Miller

The latest data from a trial that opened in 1992 confirm that for locally advanced laryngeal cancer, sequential and concomitant chemoradiotherapy each produce similar survival rates, but the concomitant approach more often allows the larynx to be preserved.

When the results of RTOG 91-11 were first published in 2003. “they changed the standard of care treatment for preserving the larynx from the sequential use of chemotherapy then radiotherapy to giving both together,” said lead investigator Dr. Arlene Forastiere of Johns Hopkins University in an email to Reuters Health.

“The results have held up over the last decade,” she said, “…and this exact treatment remains the standard of care today because on average, 15% will ultimately require laryngectomy with the concomitant approach, compared to double that, or 30%, with either giving chemotherapy and radiation in sequence or giving radiotherapy alone.”

“There’s no question that this study has changed the way we approach and treat this disease, so it is truly a landmark study,” said Dr. Chris Holsinger, a head and neck cancer surgeon at MD Anderson Cancer Center in Houston, Texas who wasn’t involved in the research.

Between 1992 and 2000, 547 patients were randomly assigned to three treatment groups: induction chemotherapy followed by radiation; concomitant chemoradiotherapy; and radiotherapy alone.

The induction group received up to three cycles of cisplatin 100 mg/m2 on day one and fluorouracil 1,000 mg/m2 per day for five days, every three weeks. Responders then received up to 70 Gy of radiotherapy in 35 treatments of 2 Gy fractions.

Those in the concomitant chemoradiotherapy group received cisplatin 100mg/m2 on days 1, 22, and 43 of radiation treatments.

Those in the radiotherapy-only group received only 70 Gy of radiation.

All of the patients had stage III or IV squamous cell cancer of the supraglottic or glottic larynx that was considered curable with laryngectomy and radiotherapy. The primary outcome measure was “laryngectomy-free survival,” which was measured after a median of 10.8 years of follow-up in the current report. Late toxicity was also measured.

Overall survival at both five and 10 years was not significantly different between any of the groups, ranging from 54%-58% and 28-39%, respectively.

There was also no significant difference in the cumulative incidence of grade 3-5 toxicities between the groups. At ten years, the rates were 30.6%, 33.3% and 38% for induction chemotherapy followed by radiation, concomitant chemoradiotherapy, and radiotherapy alone, respectively.

However, in terms of larynx preservation, there was a significant advantage for concomitant cisplatin and radiotherapy, with a 54% relative risk reduction for laryngectomy compared to radiotherapy alone (p<0.001) and a 42% reduction compared with induction chemotherapy plus radiotherapy (p=0.005).

This trial was one of the largest and longest in the field to date. But head and neck cancer is a homogenous disease. “For head and neck cancers, in general, and for larynx cancer in particular, we don’t have a fully established standard,” said Dr. Jochen Lorch, a head and neck oncologist at Dana-Farber Cancer Institute in Boston who was not involved in the trial.

“My take would be this shows value in both approaches, induction and concurrent, but I think that you’re not going to get an answer about what’s the best way to treat this disease,” said Dr. Holsinger. “I definitely think that the clear value of the different approaches also opens up the path to studying minimally invasive surgery for this disease, especially neoadjuvant approaches.”

Newer induction regimens have also further clouded the picture.

“The cisplatin and 5-fluorouracil drug combination that was used in sequence with radiation has been replaced with a more effective regimen of three drugs,” said Dr. Forastiere. “We don’t yet know whether this newer induction regimen followed by radiotherapy would be as effective as concomitant treatment. That is a study that needs to be done.”

Full results of the trial were published online November 26 in the Journal of Clinical Oncology.

Source: J Clin Oncol 2012.

November, 2012|Oral Cancer News|

Neoadjuvant chemo does not improve oral cancer survival rates

Author: DrBicuspid Staff

Patients with advanced resectable oral squamous cell carcinoma (OSCC) who undergo surgery do not benefit from improved survival after induction with docetaxel, cisplatin, and fluorouracil (TPF), according to a new study (Journal of Clinical Oncology, November 5, 2012). Study author Zhi-yuan Zhang, MD, PhD, from Shanghai Jiao Tong University School of Medicine, and colleagues assessed 256 patients with resectable locally advanced OSCC.

A total of 222 patients completed the full treatment protocol. They received two cycles of TPF induction chemotherapy (75 mg/m2 of docetaxel on day 1, 75 mg/m2 of cisplatin on day 1, and 750 mg/m2 of fluorouracil on days 1 to 5) followed by radical surgery and postoperative radiotherapy versus upfront radical surgery and postoperative radiotherapy.

The primary end point was overall survival. Secondary end points included local control and safety.

After a median follow-up of 30 months, there was no significant difference in overall survival or disease-free survival between patients treated with or without TPF induction, the study authors noted. Patients in the induction chemotherapy arm with a clinical response or favorable pathologic response had superior overall survival and locoregional and distant control.

“Our study failed to demonstrate that TPF induction chemotherapy improves survival compared with upfront surgery in patients with resectable stage III or IVA OSCC,” the authors concluded.

The lack of survival benefit indicates that TPF induction chemotherapy without selection could not benefit OSCC patients in general, Dr. Zhang told Reuters Health in a news story.

“On the other hand, superior outcomes are seen in responders, as assessed both by clinical and pathologic responses,” he said. “Therefore, induction chemotherapy is likely to be effective for biologically distinct subgroups, and biomarker development might lead to identification of patients whose tumors are likely to respond to a particular treatment.”

November, 2012|Oral Cancer News|

Study will evaluate Panitumumab regimen in advanced SCCHN

Author: staff

Canadian researchers are investigating standard fractionation radiotherapy with concurrent high-dose cisplatin versus accelerated fractionation radiotherapy with panitumumab in patients with locally advanced stage III and IV squamous cell carcinoma of the head and neck (SCCHN).

The NCIC Clinical Trials Group has completed accrual for the randomized phase III study, which has a planned sample size of 320 patients with SCC of the oral cavity, oropharynx, larynx, or hypopharynx. The trial was launched in December 2008, and the Data Safety and Monitoring Committee recommended continuing the trial in October 2011.

Patients assigned to arm I will undergo standard fractionation radiotherapy once daily, five days a week, for seven weeks; they will also receive cisplatin intravenously over one hour on days 1, 22, and 43 of radiotherapy.

Participants assigned to arm II will undergo accelerated fractionation radiotherapy once or twice daily, five days a week, for six weeks; they will also receive panitumumab intravenously over 30-90 minutes one week prior to and on days 15 and 36 of radiotherapy.

The primary endpoint is progression-free survival (PFS), while secondary endpoints include overall survival, local and regional PFS, distant metastases, adverse events, swallowing-related quality of life, functional swallowing outcomes, and economic assessments.

The FDA has approved panitumumab under the brand name Vectibix for the treatment of patients with metastatic colorectal carcinoma with disease progression on or following chemotherapy regimens containing fluoropyrimidine, oxaliplatin, and irinotecan. Panitumumab is a human IgG2 kappa monoclonal antibody that binds specifically to human epidermal growth factor receptor (EGFR).

Amgen, which markets Vectibix, has joined the Canadian Cancer Research Society Institute in supporting the trial (NCT00820248).

Waldron JN, Parulekar W, O’Sullivan B, et al. A phase III study of standard fractionation radiotherapy with concurrent high-dose cisplatin versus accelerated fractionation radiotherapy (RT) with panitumumab in patients with locally advanced stage III and IV squamous cell carcinoma of the head and neck (SCCHN) (NCIC Clinical Trials Group HN.6). J Clin Oncol. 2012;30(suppl; abstr TPS5600)

September, 2012|Oral Cancer News|