Why is chemo so nauseous?

Novel therapies for nausea and vomiting in advanced illness and supportive cancer care

https://tinyurl.com/52nu5m5z

For cancer patients on chemo one of the most distressing adverse effects is nausea and vomiting. About 50% of them experience severe nausea. Some chemo, notably the platinum drugs are even more likely to result in severe nausea, with all patients being affected to some degree. Up to 20% of them will either cease or have their treatment modified because of it. Despite this being so common the cause is little understood.

It is thought that the emetic effect of chemo is due to altered gastric and bowel transit, increased mucosal sensitivity, altered gut-brain communication or psychiatric anxiety, Support for the latter cause comes from the effectiveness of antipsychotic medication such as haloperidol in managing nausea for some patients, these drugs act to block neurotransmitter receptors.

To counter this it is now standard therapy to treat patients prophylactically with Ondansetron being the most used drug, increasingly quadruple therapy, which adds receptor blockers with steroids and anti-psychotic treatment, is employed.

Other forms of treatment are in development. These include Blonanserin an antipsychotic used trans dermally for nausea and Mirtazapine an anti-depressant. In acute presentations inhaling fumes from alcohol infused prep wipes has been shown in controlled trials to be effective and reduce drug costs, this mostly reduces nausea, less so vomiting.

Class actions, who wins?

Australian women file writ against Johnson & Johnson over link between talcum powder causing mesothelioma and cancer

https://tinyurl.com/vzvvj9yh

Class actions or contingent litigation are increasingly common and have become important sources of income for lawyers and third-party funders. This no win, no fee legal process groups together individuals who believe they have been adversely affected by the actions of big corporate business. One of the latest in Australia involves an attempt to obtain financial compensation for cancer caused allegedly by talcum powder. 1300 women have registered an interest in a case to be heard in the Victorian Supreme Court.

Defendants in the writ are the multinational Johnson and Johnson who have been subject to many similar suits in the US. They dispute the link betewen talc and cancer and deny that their product might be contaminated with asbestos, which is a well proven cause  of mesothelioma. In a recent statement the World Health Organisation has classified talc as probably carcinogenic.

The legal process in the US has been lengthy and remains incomplete. No doubt any case in Australia would be similar. Many of the women will not understand the legal delay and judging by previous similar cases, could well be disappointed with the result.

Liquid biopsy trial fail

Implosion of Grail’s Galleri Cancer Screening Test?

https://tinyurl.com/3extfeuh

One of the major goals in cancer research is to develop means of early diagnosis for cancers which typically present at an advanced stage, such as ovarian cancer. The Grail cancer screening test is one such attempt. Using circulating tumour DNA as a marker of disease, the test seeks to identify cancer early to improve survival.

This test has been applied over the last three years in the Galleri Clinical Trial in the UK. The prospective trial has 142000 participants aged between 50 and 77, with possible expansion to one million and is administered by the NHS. The key endpoint is reduction in numbers of cancers presenting on diagnosis as stage 3 or 4, with a later stated goal of fewer than 20% of cancers presenting at stage 4. The trial was controversial with complaints of poor use of limited resources and possible bias. However, political pressure in the form of honouring an electoral promise, ensured it’s commencement.

Now the test manufacturer; Grail has announced the preliminary results which show that the primary endpoint has not been achieved. This has caused a collapse in the stock price of the company and led to no further increase in participants for the NHS-sponsored test. The manufacturer claims it is too soon to evaluate the test; numbers of end stage 4 tumour diagnoses are reduced, and survival benefits will take more time to be seen. Of course they would say that wouldn’t they?

New hope for the platinum resistant

FDA approves pembrolizumab with paclitaxel for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma

https://tinyurl.com/dndxk5ea

Paclitaxel, a combination therapy of a taxane and a platinum drug for chemotherapy of ovarian cancer has been used for more than 30 years. This combination of a cytotoxic and a growth suppressant radically changed the survival for women with this disease.

Unfortunately, drug resistance to this combination especially to the platinum drug is inevitable and for some women this occurs early in the first 6 months after initial treatment, this is known as “platinum resistance”.

Platinum resistance is a grave finding and difficult to treat. Recent results from a clinical trial called KEYNOTE-B96 have shown promising response to a new combination of immunotherapy and chemo using a checkpoint inhibitor (Keytruda) together with paclitaxel with median improved overall survival of 18 months.

Previously immunotherapy with checkpoint inhibitors has not been shown to be effective for high grade serous ovarian cancer. In the context of platinum resistance there is evidence of change in the immune profile with loss of tumour suppression genetic activity and increased circulating programmed cell death protein (PD-1). It is PD-1 which is the marker of checkpoint protection of cancer cells.

Of the 643 patients in the KEYNOTE trial about 70%  were shown to be PD-1 expressers. Severe side effects meant that treatment was terminated early for 16% of those patients who received Keytruda. However, the significantly improved survival for those women in the treatment arm of the trial has prompted FDA approval of the use of Keytruda in combination with Paclitaxel for treatment of platinum resistant ovarian cancer when PD-1 expression is present.

resistant ovarian cancer when PD-1 expression is shown.

Fatal blood clot

Cancer-associated thrombosis in the era of precision oncology: Mechanisms, challenges and future directions

https://tinyurl.com/52e2xt9p

For people with cancer the risk of dying from other causes is increased. The most likely non-cancer cause of death is from thrombosis. Either arterial clot with possible stroke or infarct or venous clot with subsequent pulmonary embolus. Death from thrombosis is up to 12 times more likely for patients with cancer compared to the general population especially early, during chemo.

This review describes why cancer patients are at high risk of thrombosis; it appears there are two groups of cancers those which are at high risk of thrombosis which includes ovarian cancer patients who have a 20% risk, and those which are relatively low risk, breast cancer is in this group.

Thrombosis is a result of slow blood flow, vascular damage or increased clotting factors. Cancer increases all these hazards with some specific issues such as, platelet adhesion and increase in extracellular DNA fibres which act as a focus for blood clot, these are known as neutrophil extracellular traps (NET). As the cancer progresses and spreads the risk of thrombosis is greater.

The presence of venous clot greater decreases the survival of cancer patients. The authors suggest that thrombosis should be anticipated and prophylactic prevention should be routine for cancer patients.

Time toxicity

Health Care Contact Days in Older Adults with Metastatic Cancer

https://tinyurl.com/yjwcbcpn

Sometimes health care professionals forget or fail to recognise the impact a cancer diagnosis can have on the lifestyle of the individual affected. This retrospective study looked at the Medicare reference data for more than 50000 patients with metastatic cancer of varying types, with a comparison of the number of healthcare contact days in 2008 to the same period in 2019.

Findings from the study showed a significant change with the mean number of contact days increasing by about 50% to around 62 days each year. For some cancers, notably breast cancer, the contact days increased even more sharply.

This represents 16% or more of an individual’s already limited life expectancy; this burden on cancer patients has been labelled “time toxicity”. The authors suggest this information should be included in informed consent communication and that attempts to reduce the number of contact days, by arranging same-day appointments would improve the quality of life for cancer patients.

How ovarian cancer changes the abdomen

 

Ovarian cancer metastasis to the human omentum disrupts organ homeostasis and induces fundamental tissue reprogramming

https://tinyurl.com/ydth346z

One of the most important factors which determine whether women are cured of ovarian cancer is the completeness of the initial surgery. A multi-specialist intervention is now common with surgical oncologists co-operating with gastro -intestinal and renal surgeons to ensure clearance of the cancer. Despite this many women with ovarian cancer who are deemed to have had complete clearance will have tumour recurrence and die.

This research suggests that a reason for this is a change in the tumour microenvironment caused by metastasis to the omentum. Commonly known as the abdominal policeman, the omentum is formed in two parts early in embryological development, the greater omentum is a fold of peritoneum attached to the stomach and colon, the lesser omentum lies between the stomach and liver covering the kidneys and pancreas. Its function is complex partly acting to contain infection and promote immune defence against cancer.

In this small study, samples of the greater and lesser omentum were taken from patients, with and without ovarian cancer and examined to determine any difference. Findings from the study suggest that the omentum loses protective capacity with damage to the normal immune response to cancer. This finding suggests that more extensive surgery particularly involving the lesser omentum may be required for complete clearance. This would increase peri-operative mortality and morbidity.