Tag: colon cancer

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Game-changing Therapy Targets Colon Cancer that has Spread to the Liver

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Source: CC0

Physicians at Cedars-Sinai Cancer are now using a unique therapy, called hepatic artery infusion (HAI) pump chemotherapy, that offers hope to colorectal cancer patients whose disease has spread and who now have inoperable liver tumours. The system, which was developed over two decades ago, is only now being adopted more widely, also spares the rest of the body from much of the chemotherapy drugs’ toxicity.

“Many of these patients are not candidates for curative surgery and we now have a meaningful option for treating them,” said Cristina Ferrone, MD, chair of the Department of Surgery at Cedars-Sinai and a specialist in the care of patients with complex hepato-pancreato-biliary disorders. “This therapy has been shown to extend both life and quality of life.”

Colorectal cancer is the fourth-leading cause of cancer-related death in the US. In as many as 25% of patients diagnosed with the disease, the cancer spreads to the liver, where it can be difficult to treat. However, more than half of patients receiving hepatic artery infusion pump therapy go on to receive curative surgery, studies have shown.

Cedars-Sinai Cancer and associate professor of Surgery at Cedars-Sinai, sat down with the Cedars-Sinai Newsroom to explain this lifesaving therapy.

How do the pumps work?

We surgically place the pump underneath the skin, outside of the abdominal cavity, and it is attached to tubing that enters the abdominal cavity and goes into the gastroduodenal artery. That artery feeds into the hepatic artery, which supplies blood to the liver. During surgery, we block blood flow from the gastroduodenal artery from going into portions of the small intestine so that the therapy flows only to the liver.

The pump has a soft centre, allowing its internal reservoir to be filled through the skin via a syringe. After surgery, the patient comes in every two weeks and we refill the pump, which then allows the chemotherapy drug to flow directly into the liver via the arterial supply.

Which patients are likely to benefit from hepatic artery infusion pump therapy?

This therapy is designed for patients, based on the distribution of the metastatic disease (where are the tumours and how many), for whom curative surgery is not an option at the time of diagnosis. The best we had been able to offer these patients was lifelong chemotherapy that had potential systemic toxicities, and that never quite reduced their tumour size to the point that we could surgically remove it. This therapy offers an additional option for liver-directed therapy that can potentially make patients candidates for surgery by specifically targeting the liver disease.

What are the advantages of the hepatic artery infusion pump over traditional chemotherapy delivery?

A majority of these tumours derive their blood supply from the hepatic arterial system, and delivering chemotherapy to the tumours through the hepatic arterial system allows us to give higher doses of specific chemotherapeutic agents without exposing the patient to their systemic toxicities. Data shows that up to 60% of appropriately selected patients receiving hepatic artery infusion pump chemotherapy were then able to receive curative surgery. Patients can often continue receiving systemic chemotherapy in combination with hepatic artery infusion pump chemotherapy.

Are hepatic artery infusion pumps used to treat other types of liver cancer?

Some patients with cholangiocarcinoma are currently treated with HAI pumps, but this is not yet standard of care. Colon cancer is the second most common cancer, and colon cancer that has metastasized to the liver affects a significant number of patients. And we have seen good outcomes with those patients. Other types of cancers that metastasise to the liver are significantly more challenging to treat, and thus far, we don’t think this therapy will benefit those patients.

Is this a new therapy?

Hepatic artery infusion pumps have actually been around for about 25 to 30 years, but until quite recently only a few medical centres were using them. But more and more centres are realising that this therapy can truly benefit patients, and it is becoming more widely available.

Source: Cedars-Sinai Medical Center

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‘Striking’ Colon Cancer Trial Data gets Standing Ovation

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Woman using lab equipment
Source: NCI on Unsplash

In a clinical trial, nearly every one of the 112 patients with mismatch repair-deficient (dMMR) colon cancer achieved a pathologic response with just two cycles of neoadjuvant immunotherapy, prompting a presentation panellist to describe it as “striking data” – though a note of caution was given.

Patients in the NICHE-2 single-arm study received PD-1 plus CTLA-4 blockade – nivolumab plus ipilimumab, and successfully underwent surgical resection, 98% on time, meeting the study’s primary safety endpoint, reported Myriam Chalabi, MD, at the at the European Society for Medical Oncology (ESMO) annual congress.

And with a median follow-up of 13.1 months, the disease-free survival (DFS) rate was 100%, said Dr Chalabi of the Netherlands Cancer Institute in Amsterdam. She pointed out that, by this point, the expected rate for this patient population was about 15%. The primary efficacy endpoint for the trial is DFS at 3 years, with success defined as a rate of 93% (data are expected next year).

A standing ovation erupted when Dr Chalabi displayed the waterfall plot showing the depth of pathologic response with just four weeks of nivolumab plus ipilimumab.

Credit: NICHE-2 Study

Among the 107 patients evaluable for efficacy, all but one had a pathologic response, 95% had a major pathologic response (MPR), and 67% had a pathologic complete response (pCR), ie no residual viable tumour in both the primary tumour bed and lymph nodes.

“As you can appreciate, the pathologic regression observed was near-complete or complete in almost all patients,” she said.

In contrast, pathologic response rates in the range of 5% to 7% for this population have been shown in prior trials involving neoadjuvant chemotherapy, said Chalabi.

Some 10–15% of colon cancers are classified as dMMR, she explained, which are highly sensitive to immune checkpoint inhibitors, where a number of agents have been approved for the metastatic setting.

The first to comment in Q&A, Alexander Eggermont, MD, PhD, stressed the potential impact of the findings, saying that patients with dMMR tumours scheduled for resection “should be taken off the surgical program.”

“They should be sent to the medical oncologist for the first dose of ipi/nivo,” he said. “We will live the day that they will not undergo surgery anymore after these schedules – that’s the next step.”

A multicentre, single-arm study, NICHE-2 enrolled 112 patients with previously untreated non-metastatic dMMR colon cancer undergoing surgery. The first cycle of neoadjuvant treatment included ipilimumab (1mg/kg) and nivolumab (3mg/kg). The second cycle, given two weeks later, was limited to nivolumab alone. After the first dose, median time to surgery was 5.4 weeks.

The trial defined pathologic response as 50% or less residual viable tumour; MPR was defined as 10% or less residual viable tumour, and included patients with pCRs in the primary tumour but viable tumour in the lymph nodes.

The median age of patients was 60, and 58% were women. About three-fourths had high-risk stage III disease, 13% had low-risk stage III disease, and 13% had stage I/II disease. About half had radiologic high-risk disease (both T4 and N2), said Dr Chalabi, and abdominal wall involvement was common.

When asked whether randomised data would be needed to make this approach standard, Dr Chalabi pointed out the group with T4 tumours.

“I wouldn’t want to randomise those patients,” she said. “Surgeons usually would prefer to have some type of downstaging before continuing on to surgery in order to increase the chances of achieving tumour-free resection margins and also to limit the extent of surgery needed to achieve that.”

The case for randomisation is stronger in earlier disease, she said, but if recurrences can be prevented even in stages where recurrence is more rare, such as stage II tumours (about 10% at 3 years), “we’re curing 10% more patients.”

A little less than a third of patients had Lynch syndrome, and pCRs were more frequent in this subset (78% vs 58% in those with sporadic tumours). Immune-related adverse events (AEs) were reported in 61% of patients, with 4% being grade 3/4.

When the prospect of a NICHE-3 trial came up, Dr Chalabi said that it ideally would have been an international study to validate the approach. However, a subsequent trial is being developed and will likely involve nivolumab plus anti-LAG-3 relatlimab, “which is a shame,” she noted.

“If we do get similar responses with nivolumab and anti-LAG-3, then that may be an avenue to test organ-sparing approaches with that combination in this population,” she added.

Source: MedPage Today

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Compound in Chinese Herbal Medicine May Prevent Colon Cancer

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Colon cancer cells
Colon cancer cells. Source: National Cancer Institute on Unsplash

Emodin, an active compound found in Chinese herbal medicine, can prevent colon cancer in mice, according to researchers, and may be applicable in humans as well, a study has found. The mechanism behind this is likely emodin’s ability to reduce the number of pro-tumour macrophages.

The study is published in the American Journal of Physiology-Gastrointestinal and Liver Physiology.

Emodin, a major bioactive anthraquinone derivative extracted from rhubarb, represents multiple health benefits in the treatment of a host of diseases, such as immune-inflammatory abnormality, tumor progression, bacterial or viral infections, and metabolic syndrome. Emerging evidence has made great strides in clarifying the multi-targeting therapeutic mechanisms underlying the therapeutic efficacy of emodin, including anti-inflammatory, immunomodulatory, anti-fibrosis, anti-tumor, anti-viral, anti-bacterial, and anti-diabetic properties.

Besides investigating if emodin could prevent colon cancer, the study’s researchers especially wanted to know whether its anti-cancer properties “could be attributed to its actions on immune cells and particularly macrophages,” said Angela Murphy, PhD, co-author of the study. In this murine model, emodin was shown to reduce both polyp count and size. Also, mice treated with emodin “exhibited lower protumorigenic M2-like macrophages in the colon,” researchers wrote in the study.

Roughly 70% of colon cancer cases can be attributed to diet or other lifestyle factors, said Dr Murphy. Because emodin is also found in some fresh fruits and vegetables, it is hoped that consuming these emodin-containing foods could prevent colon cancer in humans.

Source: American Physiological Society