Chemotherapy Before Surgery Improves Outcome In Nonsmall Cell Lung Cancer
Main Category: Lung CancerArticle Date: 20 Jul 2007 - 5:00 PDT
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Combining pre-operative chemotherapy and surgery increases the average chance of survival at five years by approximately 6% compared with surgery alone.
This conclusion was drawn by a team of Cochrane Researchers from the MRC Clinical Trials Unit in London after they identified 12 eligible randomised controlled trials. Data from seven of these trials were available from trial reports and were combined in a meta-analysis. The seven trials involved a total of 988 patients.
"This is currently the best estimate of the effectiveness of this therapy, but is based on a relatively small number of trials and patients," says lead researcher Sarah Burdett.
There was, however, insufficient data to break the patients down into sub-groups and see whether the effectiveness varies for different types of patients or stages of the disease.
This research is important because around the world more than a million new cases of lung cancer are diagnosed each year, around 80% of which are non-small cell lung cancer. In addition, many patients are only diagnosed after the disease has progressed, so survival rates across all stages of disease tend to be fairly low at around 14%, with only a quarter of patients being suitable for surgery.
The Cochrane Systematic Review found that using chemotherapy before surgery can reduce the size of tumours making the surgery simpler, and increasing the number of patients who may be candidates for surgery. The worry is, however, that having a course of chemotherapy delays the operation, and could therefore leave patients at risk of allowing the tumour to spread.
"The data suggest that the benefits of the chemotherapy outweigh the risks associated with the delay," says Burdett
A project to collect complete data on all patients included in all trials is ongoing and will be able to fully assess the value of this treatment.
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Source: Jennifer Beal
John Wiley & Sons, Inc.
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Chemotherapy Can Compliment Surgery
posted by Gregory D. Pawelski on 28 Jul 2007 at 7:24 pmThe first question to ask the proponents of using pre-surgery chemotherapy, what happens when the empiric chemotherapy chosen is "resistant" to the cancer cells? Just switch drugs if the tumor does not respond to treatment?
In patients with cancer, it is often difficult to select an effective first-line treatment because tumor can develop resistance to many drugs. Currently, physicians select an empirically-selected drug and must wait about six months to see whether it is effective on a particular patient. Pre-surgical chemotherapy could shorten this time period, but nonetheless, a chain reaction could already be occurring.
A chemo-induced gene mutation can happen when the original chemo received does not work. The cancer comes back or doesn't go anywhere. When it does this, the cancer comes back more aggressively or becomes more aggressive. The mutagenic effects (changes in form) of chemotherapy on a genetically-unstable tumor, drives the tumor into a state of more aggressive behavior. You might kill off a whole lot of cancer or not at all, only to cause a mutation in the remaining cancer, such that the remaining cancer behaves in a more aggressive fashion, and surgery cannot go after those aggressive cancer cells.
Cancers that are a product of these genetic mutations release cells from the usual controls of proliferation and survival, making them so much harder to fight it. Following this mutation, the cancer cells acquire the ability to proliferate without the normal restraints. As the cancer grows, it may infiltrate and destroy the surrounding tissue, and metastasize by penetrating into blood vessels, lymph nodes, and body cavities. Distant metastasis via the bloodstream may affect virtually any organ (the lungs, bones, liver, adrenals, and even the brain).
A failed attempt at chemotherapy is detrimental to the physical and emotional well being of patients, is financially burdensome, and may promote the onset of clinically acquired multi-drug resistance. It would be highly desirable to know what drugs are effective against particular cancer cells "before" these toxic agents are systemically administered.
Some researchers believe the reason for better survival for patients who could undergo complete resection without any tumor left behind is that these tumors are biologically less aggressive and would do better regardless of the type of treatment they receive, and that the removal of lymph nodes at the time of surgery may additionally contribute to a better outcome. Surgery is an integral part of the multimodality treatment of many cancers, "before" chemotherapy.
The line of reasoning frequently used to explain the value of surgery included five points: First, surgery is thought to remove resistant clones of tumor cells and thus decrease the likelihood of the early onset of drug resistance. Second, the removal of large masses likely to be associated with poorly vascularized areas of tumor improves the probability of delivering adequate drug doses to the remaining cancer cells. Third, the higher growth fraction in better vascularized small masses enhanced the effect of chemotherapy. Fourth, smaller masses required fewer cycles of chemotherapy and thus decreased the likelihood of drug resistance. Fifth, removal of bulky disease enhances the immune system.
Sources:
Mayo Clinic
American Board of Surgeons
Society of Surgical Oncology
Thomas A. d'Amato, et al, Thorac Surg Clin 17 (2007) 287-299
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