Chemotherapy, locoregional

Options for stage I and II follicular lymphoma include locoregional radiation therapy, chemotherapy followed by radiation therapy, and extended-field radiation therapy. 

Pignon JP, Bourhis J, Domenge C, Designe L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 2000 ... 

The Northern California Oncology Group randomized 104 patients with unresectable disease to standard daily radiation therapy with or without concomitant bleomycin (5-FU iv twice weekly) followed by 16 wks of adjuvant chemotherapy (methotrexate 25 mg/m2 weekly) after the completion of radiation therapy (22). A locoregional CR of 67% was seen in the concomitant arm vs 45% in the control arm (p = 0.056). The 2-yr locoregional control rate was 64% vs 26% (p = 0.001) and the development of metastases was 38% vs 24% (p > 0.25), respectively. 

An early trial sponsored by the National Cancer Institute of Canada failed to establish a significant difference in locoregional control and overall survival when evaluating 212 patients with larnygeal or hypopharyngeal squamous cell carcinoma (SCCA) treated with 50 Gy in 20 fractions over 28 d or split-course radiotherapy of 25 Gy in 10 fractions over 14 d, followed by a 28-d rest and then 25 Gy in 10 fractions over 14 d beginning on d 43 with mitomycin C (10 mg/m2 on d 1 and 43) in combination with continuous infusion 5-FU (1000 mg/m2/d on d 1-4 and 43-46) (48). Nevertheless, this study suggested that the addition of chemotherapy may overcome the decreased activity of split-course radiotherapy. 

The largest meta-analysis is the Meta-Analysis of Chemotherapy in Head and Neck Cancer (MACH-NC) study evaluating 63 trials with a total of 10,741 patients (Table 2) (69). MACH-NC assessed individual data rather than literature-based data with the inclusion of updated data and unpublished trials. For two-thirds of the trials, individual data were updated to a median follow-up of 6.8 yr. The meta-analysis was subcategorized into locoregional treatment with and without concomitant chemotherapy, induction/adju-vant chemotherapy, and laryngeal preservation with induction chemotherapy rather than definitive treatment for laryngeal and hypopharyngeal tumors. 

El Sayed and Nelson reviewed 42 trials between 1963 and 1993 including six trials prior to 1965 and one trial using razoxane, a nonstandard chemotherapy agent (73). A drawback to the El Sayed analysis is the inclusion of a single trial that had been accounted for twice because of its publication in two different journals. The addition of chemotherapy to locoregional treatment added an absolute benefit of 4.0% absolute benefits of concomitant chemotherapy were 8% (neoadjuvant and adjuvant chemotherapy were not assessed). 

Radiation therapy s main role is in the treatment of LD. Because radiation only offers locoregional control, chemotherapy is necessary to destroy the micrometastatic disease that invariably is present. Multiple cooperative group trials have been performed to establish the role of radiation therapy in SCLC (3-7). 

Because patients with very severe social problems tend to be excluded from prospective trials, additional problems may emerge now that many clinicians have accepted chemoradiation as the standard treatment for locoregionally advanced disease. There is no evidence that the use of concurrent chemotherapy permits significant reductions in total treatment dose there is also no evidence that chemoradiation overcomes the detrimental effects of treatment protraction. It is therefore critical that multidisciplinary teams work closely with patients and social services to educate patients and facilitate the timely and complete administration of this complex treatment. 

The clinical advantages of Ad-p53 are its tumor-selective mechanism of action and low toxicity profile that allow combinations with conventional chemotherapy and radiation therapy. The limitations are the locoregional delivery and inability to target metastatic disease. Clearly, early-stage patients who cannot tolerate surgery because of poor pulmonary function or other comorbidities and would be treated with radiation therapy alone may represent a subset that would benefit from the addition of Ad-p53 to radiation therapy. 

In recent therapy assessment studies promising results with [ F]FET-PET have been obtained. Sequential p F]FET-PET studies during locoregional chemotherapy and radioimmunotherapy show a high correlation between the [ F]FET uptake and the response of the tumor to treatment [213,214]. 

Direct randomized comparisons unfortunately are very rare. However, the two Stockholm breast cancer trials in women treated with modified radical mastectomy provide a comparison of postoperative radiotherapy and chemotherapy with a median follow-up of 18 years (Rutqvist and Johansson 2006). All patients had node-positive disease or a tumor diameter exceeding 30 mm. The radiation dose was 46 Gy in 2-Gy fractions to the chest wall, axilla, supraclavicular fossa, and the ipsilateral internal mammary nodes. Ghemotherapy initially consisted of 12 cycles (later 6 cycles) of cyclophosphamide 100 mg/m orally on days 1-14, methotrexate 40 mg/m i.v. on days 1 and 8, and 5-fiuorouracil 600 mg/m i.v. on days 1 and 8 (CMF). In the trial that included premenopausal patients, 291 were allocated to CMF and 256 to radiotherapy. In each arm, 12% were node negative. Sixty-two and 64% were estrogen-receptor positive, respectively. Locoregional recurrence was observed in 14% after radiotherapy and 24% after chemotherapy (hazard ratio 0.67, p = 0.048). The absolute benefit increased with the number of positive lymph nodes. As might be expected, fewer patients developed distant recurrence after CMF and the eventual difference in breast cancer deaths was 50% versus 56%. This... 

A Step Towards Supraconservative Surgery 103 Interventional Procedures for the Locoregional Treatment of Breast Cancer 105 Percutaneous Imaging-Guided Tumor Ablation 105 Intraarterial Infusion Chemotherapy 106 References 106... 

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