Advances in Chemotherapy Treatments for Cancer: Promising Results with Paclitaxel

Many millions of cancer cases are diagnosed around the world each year. A combination of surgery, radiotherapy and/or chemotherapy can be used to treat cancer. Paclitaxel (Anzatax) belongs to a group of medications known as the taxoid drugs, or taxanes. They are called antineoplastic (ie, working against neoplasms, another term to describe cancers or tumours) medications and act to kill and destroy the cancer cells as they grow. During the growth process, cancer cells pass through a series of stages in the cell cycle. Paclitaxel acts to stop the cancer cells during a specific stage, so that the abnormal cancer cells cannot continue to grow and divide.

Paclitaxel has shown promising results in treating specific types of cancer, and is now used in ovarian, breast, non small cell lung, and some head and neck cancers. Multiple studies have demonstrated the improvement paclitaxel offers in both morbidity and mortality rates. In the last ten years, these benefits in clinical trials have been recognised by the Pharmaceutical Benefits Scheme (PBS) and the medication is approved and subsidised for the treatment of primary and advanced ovarian cancer after standard treatment has failed, advanced breast cancer that has spread, and also, in conjunction with other agents, to treat certain types of breast cancer. Breast CancerAdjuvant treatmentPaclitaxel in combination with other medications, called adjuvant treatment, has been extensively studied and investigated in many clinical trials. It is very active against cancer cells, and has improved survival rates in patients with metastatic breast cancer (ie cancer that has spread).A trial known as the CALGB (Cancer and Leukaemia Group B) 9344 was conducted in 3,170 women with primary breast cancer that had spread to the lymph nodes (these are small round structures that are part of the lymphatic system and help filter micro-organisms and toxins from the body, through which white blood cells also travel). These women were further divided into those who had breast cancers with oestrogen receptors and those without oestrogen receptors. The effects of 4 cycles of increasing doses of doxorubicin (another chemotherapy drug which interacts with DNA) combined with cyclophosphamide and with or without 4 cycles of paclitaxel were evaluated. There were significant changes at 52 months follow-up, compared with at 21 and 30 months. Patients who received paclitaxel treatment had an improved rate of disease-free survival. The disease-free survival rate at 48 months follow-up for patients treated with paclitaxel was 73%, versus 70% for those treated with cyclophosphamide alone. The study also showed that paclitaxel treatment has the greatest benefit in patients with tumours which did not have oestrogen receptors.Anthracycline-Taxane CombinationsWhen breast cancers have spread to other parts of the body, the usefulness of treatments such as surgery and radiation therapy are limited. Chemotherapy is a useful option in these cases. Many studies have investigated the use of paclitaxel in the treatment of cancer cases that have spread beyond the breast. Paclitaxel has often been used in conjunction with another group of medications called anthracyclines (such as doxorubicin and daunorubicin) when anthracycline medications alone failed to treat metastatic disease. Therapy with paclitaxel as a second line single agent after doxorubicin failure has been studied in several randomised trials. Response rates ranging from 16% to 32% were seen.Neoadjuvant Therapy Neoadjuvant chemotherapy refers to the use of medications to treat or shrink the primary cancer so that later treatments such as surgery are more effective. Taxanes have been used in this setting, both as a single agent and in combination with other agents. Improved response rates and opportunities for the breast to be conserved have been demonstrated. One trial investigated 350 patients who had their primary breast tumour surgically removed, and were then randomised to either eight cycles of treatment with chemotherapy agents known collectively as FAC (5-fluorouracil, Adriamycin, and cyclophosphamide), or four cycles of paclitaxel followed by four cycles of FAC. After four years, there was a 24% reduction in the risk of recurrence with the combination of paclitaxel and FAC.Paclitaxel versus DocetaxelA recent trial conducted by the North American Breast Cancer Intergroup E1199 compared two medications that belong to the taxane group, paclitaxel and docetaxel. Between 1999 and 2002, 4,988 women with breast cancer that had spread to the lymph nodes, or those at high risk of the cancer spreading to the lymph nodes, were recruited for the study. All patients received 12 weeks of doxorubicin and cyclophosphamide. After this course of treatment, patients were divided into four groups to receive either: paclitaxel each week, paclitaxel every three weeks, docetaxel each week, or docetaxel every three weeks. Results of the study were in keeping with previous conclusions that taxanes are beneficial in prolonging survival. There were no significant differences between paclitaxel and docetaxel in terms of survival rates, but docetaxel was associated with more potentially dangerous side-effects.Head and Neck CancersNew hope has been provided for patients with head and neck cancers where the cancer has spread and invaded local structures in the body. Research has shown that adding paclitaxel to the usual chemotherapy treatment is associated with an increased response rate in up to one third of these cases. The preservation of the ability to speak and swallow has also been demonstrated. This allows patients who suffer from head and neck cancers to retain these vital functions and enjoy a better quality of life. In a recent clinical study, 384 patients with locally advanced head and neck cancers were randomised to treatment with either cisplatin on day 1 plus a continual infusion of 5-Fluorouracil (5-FU) for five days every three weeks, or the same treatment plus paclitaxel on day 1 of each cycle.Tumours resolved in 32% of patients who received the triple. Chemotherapy with cisplatin and 5-FU alone was associated with a complete response rate in only 13%. The progression of head and neck cancer was postponed to approximately 23 months in patients receiving the paclitaxel combination. This is in comparison to 18 months seen for patients treated with the conventional medications. In relation to benefits on quality of life, parts of the mouth and digestive tract (including the larynx, pharynx, and tongue) were preserved in 88% of patients who received the paclitaxel combination, compared with 75% of those who were treated with cisplatin and 5-FU alone. Drug eluting StentsDiseases of the heart and its blood vessels are one of the leading causes of morbidity and mortality in our society today. Due to advances in surgical techniques and the early recognition of heart attacks and their warning signs, many patients are now receiving localised stenting to these blood vessels supplying the heart. A major concern with these stents has always been the risk of clots or blockages occurring in the stents. Patients with diabetes, blood vessels that are thin and narrow or have long, twisting lesions are most at risk. This has led to the development of drug eluting stents, which are coated with a medication to help prevent clots from forming.Recent randomised trials have demonstrated that drug eluting stents are undeniably associated with a reduced risk of narrowing and blockage. Paclitaxel is an agent that has been commonly applied to drug eluting stents. A review was conducted involving seven trials that assessed paclitaxel or sirolimus drug eluting stents versus bare metal stents (metal stents without a drug coating) in patients with disease and build up of plaques on heart blood vessels. Outcomes such as stent clotting/blockage, heart attacks, needing more extensive heart surgery such as coronary artery bypass grafting, and mortality rates were examined.Results from the study provided strong evidence that drug eluting stents reduce the risk of revascularisation (development of new, alternate blood vessels) at 12 months by 71-80%, compared with bare metal stents, in patients with lesions confined to one major coronary blood vessel. Results from patients in high risk groups also supported these findings. However, secondary outcomes such as rates of stent clotting/blockage and heart attacks did not differ by stent type. There are still issues with drug eluting stents, such as cost and potential benefits on overall patient mortality, that need to be addressed in the longer term.Ovarian cancersOvarian cancer, silent until the later stages, is often associated with a poorer outcome due to delayed diagnosis. There have been improvements in overall survival rates, partly due to advances in cancer medications. Many studies have been conducted to assess the effectiveness of chemotherapy treatments in patients with ovarian cancer. The cisplatin-paclitaxel combination has been shown to be superior to the cisplatin-cyclophosphamide combination, as it is more effective and associated with less toxic side effects. Due to the response rate seen with paclitaxel in ovarian cancers, this medication has been combined with both cisplatin and carboplatin. Both combinations have been shown to be equally effective in treating cases of ovarian cancer, although the carboplatin-paclitaxel combination is associated with less adverse effects. Non-Small Cell Lung Cancers (NSCLC)This is a particular subgroup of lung cancers that is associated with poor response rates to radiotherapy, and is unlikely to be amenable to surgery. The effectiveness and tolerability of following platinum-based chemotherapy with paclitaxel in cases of progressive NSCLC are being further investigated. A recent study has been conducted on the safety and effectiveness of a combination of celecoxib (celebrex) (an anti-inflammatory medication) and weekly paclitaxel as a second line treatment for NSCLC. 58 patients diagnosed with NSCLC that had not responded to platinum-based chemotherapy were enrolled in the study. Weekly doses of paclitaxel were administered, in combination with twice daily doses of celecoxib, for 8 week cycles. Results showed a mean progression-free survival of five months, and an overall average survival period of eleven months. One year survival rates were seen in 42.5% of the patient group. In summary, the combination of celecoxib and weekly paclitaxel was found to be an effective and relatively safe option in the treatment of progressive NSCLC. However, further clinical trials involving larger groups of patients and randomised treatments need to be conducted.