Addition Of Neoadjuvant Chemotherapy Research Articles

Therapy of invasive bladder cancer

Effective treatment of invasive bladder cancer depends upon an understanding of the natural history of this disease and careful clinical staging. Radical cystectomy offers acceptable long-term survival for most individuals with organ-confined disease, but those with more advanced tumors or those associated with adverse features may benefit from the addition of neoadjuvant chemotherapy.

Neoadjuvant chemotherapy prior to preoperative chemoradiation or radiation in rectal cancer: should we be more cautious?

Neoadjuvant chemotherapy (NACT) is a term originally used to describe the administration of chemotherapy preoperatively before surgery. The original rationale for administering NACT or so-called induction chemotherapy to shrink or downstage a locally advanced tumour, and thereby facilitate more effective local treatment with surgery or radiotherapy, has been extended with the introduction of more effective combinations of chemotherapy to include reducing the risks of metastatic disease. It seems logical that survival could be lengthened, or organ preservation rates increased in resectable tumours by NACT. In rectal cancer NACT is being increasingly used in locally advanced and nonmetastatic unresectable tumours. Randomised studies in advanced colorectal cancer show high response rates to combination cytotoxic therapy. This evidence of efficacy coupled with the introduction of novel molecular targeted therapies (such as Bevacizumab and Cetuximab), and long waiting times for radiotherapy have rekindled an interest in delivering NACT in locally advanced rectal cancer. In contrast, this enthusiasm is currently waning in other sites such as head and neck and nasopharynx cancer where traditionally NACT has been used. So, is NACT in rectal cancer a real advance or just history repeating itself? In this review, we aimed to explore the advantages and disadvantages of the separate approaches of neoadjuvant, concurrent and consolidation chemotherapy in locally advanced rectal cancer, drawing on theoretical principles, preclinical studies and clinical experience both in rectal cancer and other disease sites. Neoadjuvant chemotherapy may improve outcome in terms of disease-free or overall survival in selected groups in some disease sites, but this strategy has not been shown to be associated with better outcomes than postoperative adjuvant chemotherapy. In particular, there is insufficient data in rectal cancer. The evidence for benefit is strongest when NACT is administered before surgical resection. In contrast, the data in favour of NACT before radiation or chemoradiation (CRT) is inconclusive, despite the suggestion that response to induction chemotherapy can predict response to subsequent radiotherapy. The observation that spectacular responses to chemotherapy before radical radiotherapy did not result in improved survival, was noted 25 years ago. However, multiple trials in head and neck cancer, nasopharyngeal cancer, non-small-cell lung cancer, small-cell lung cancer and cervical cancer do not support the routine use of NACT either as an alternative, or as additional benefit to CRT. The addition of NACT does not appear to enhance local control over concurrent CRT or radiotherapy alone. Neoadjuvant chemotherapy before CRT or radiation should be used with caution, and only in the context of clinical trials. The evidence base suggests that concurrent CRT with early positioning of radiotherapy appears the best option for patients with locally advanced rectal cancer and in all disease sites where radiation is the primary local therapy.

Chemotherapy and high–dose-rate brachytherapy in the management of advanced cancers of the nasopharynx: clinical impact of high technology—is it worth the cost?

Purpose: The aim of this study was to calculate the costs of chemotherapy and high–dose-rate brachytherapy in advanced-stage nasopharyngeal cancer. It is argued whether the effect of chemotherapy and this type of high-dose, high-precision radiation therapy is worth the costs. Methods and Materials: Clinical results of Stage III–IVB nasopharyngeal cancer in patients treated between 1991 and 2000 are reported. Treatment was broken down into five categories: workup, chemotherapy, preparation of radiation therapy, and application of radiation. For each category, costs were computed. Nasopharyngeal cancer treatment costs were compared with costs previously reported on patients treated for cancers of the oral cavity, larynx, and oropharynx. Results: With the addition of neoadjuvant chemotherapy and high cumulative doses of radiation (77–81 Gy) with brachytherapy, disease-free survival increased from 48% to 74% ( p = 0.002), and overall survival increased from 35% to 72% ( p = 0.005). The Rotterdam protocol has been implemented stepwise: as of 1991, costs per patient increased from 4521 Euros (US$5023; 2001 exchange rate [December]: 1 Euro ~ 0.88 US$) for conventional external beam radiation therapy to 13,728 Euros (US$15,253) in 2000 for combinations of chemotherapy, conventional external beam radiation therapy, and brachytherapy. In case of stereotactic radiotherapy, the cost was 14,516 Euros (US$16,495). Conclusions: Costs for cancer in the nasopharynx vary from 14,528 Euros (US$16,509) to 15,316 Euros (US$17,405) in case of brachytherapy and stereotactic radiotherapy, respectively, if follow-up costs are added. The treatment cost for other head and neck sites was 21,858 Euros (US$24,126). Given the improvement in survival, the sparing capabilities of current high-dose, high-precision radiotherapy techniques, and the favorable cost profile compared with other sites, it is argued that costs should not be considered prohibitive for the introduction of chemotherapy and high–technology-based radiotherapy in advanced nasopharyngeal cancer.

Neoadjuvant chemotherapy and radiation for inoperable carcinoma of the maxillary antrum: a matched-control study.

A matched-control study comparing standard radiotherapy versus neoadjuvant chemotherapy and radiation was undertaken to clarify the effects of neoadjuvant systemic chemotherapy for locally advanced squamous cell carcinoma of the maxillary antrum. Thirty-four patients with inoperable maxillary cancer were treated with neoadjuvant chemotherapy and radiotherapy (Group II). Before starting radiotherapy, all patients in Group II received two or three cycles of neoadjuvant chemotherapy consisting of cisplatin and a 5-day continuous infusion of 5-fluorouracil with or without intravenous injection of vinblastine. Radiation doses ranged from 66 Gy to 75 Gy (median, 70 Gy). The response rate, patterns of failure, toxicity, and survival for Group II were compared with those for 34 stage-matched patients treated with radiation alone (Group I). Despite a higher response rate to neoadjuvant chemotherapy, the recurrence rate and patterns of treatment failure were not influenced by the addition of neoadjuvant chemotherapy. In most cases, neoadjuvant chemotherapy did not interfere with subsequent radiotherapy, and radiation-induced late complications occurred equally in both treatment groups. After a median follow-up of 48 months, there was no significant difference in 5-year actuarial survival or disease-free survival between the two treatment groups. Radiation alone for inoperable maxillary cancer was clearly suboptimal for improving local control and survival rate, but neoadjuvant chemotherapy in addition to standard radiotherapy failed to demonstrate any therapeutic advantage over radiation alone.