Combined Chemotherapy with Radiotherapy

Herskovic A, Martz K, al-Sarraf M, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 1992 326 1593-1598. 

Boiardi A, Silvani A, Pozzi A, et al. Advantage of treating anaplastic gliomas with aggressive protocol combining chemotherapy and radiotherapy. JNeurooncol 1997 34 179-185. 

In the majority of patients, this cancer remains occult and becomes symptomatic after it has already metastasized to the peritoneal cavity. At this stage, it usually presents with malignant ascites. It is important to accurately stage this cancer with laparoscopy, ultrasound, and CT scanning. Patients with stage I disease appear to benefit from whole-abdomen radiotherapy and may receive additional benefit from combination chemotherapy with cisplatin and cyclophosphamide. 

Both the NCCN and ASCO guidelines recommend the use of platinum-based (cisplatin or carboplatin) chemotherapy for unresect-able NSCLC. Duration of treatment with combination chemotherapy plus radiotherapy for advanced-stage NSCLC should be a minimum of two cycles to a maximum of eight cycles in most cases. - ... 

Herskovic, A., Martz, K., al-Sarraf, M., Leichman, L., Brindle, J., Vaitkevicius, V, Cooper, J., Byhardt, R., DavLs, L., and Emami, B. (1992). Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N. Engl. J. Med. 326, 1593-1598. 

Cancer treatment is a multimodality treatment, i.e., surgery is combined with radiotherapy and antineoplastic chemotherapy. The latter treatment mode is used mainly for cancers which have disseminated. Different forms of cancer differ in their sensitivity to chemotherapy with antineoplastic agents. The most responsive include lymphomas, leukemias, choriocarcinoma and testicular carcinoma, while solid tumors such as colorectal, pancreatic and squamous cell bronchial carcinomas generally show a poor response. The clinical use of antineoplastic agents is characterized by the following principles. 

Cytotoxic chemotherapy is the treatment of choice for chemotherapy-sensitive tumors such as SCLC and lymphoma. As indicated earlier, chemotherapy also may be combined with radiotherapy, especially in patients with lymphoma who have bulky mediastinal lymphadenopathy. 

An alternative anti-cancer strategy entails insertion of a copy of a tumour suppresser gene into cancer cells. For example, a dehciency in one such gene product, p53, has been directly implicated in the development of various human cancers. It has been shown in vitro that insertion of a p53 gene in some p53-dehcient tumour cell lines induces the death of such cells. A potential weakness of such an approach, however, is that 100 per cent of the transformed cells would have to be successfully treated to fully cure the cancer. Tumour suppressor-based gene therapy in combination with conventional approaches (chemotherapy or radiotherapy) may, therefore, prove most efficacious, and the sole gene-therapy-based medicine approved to date (in China only) is based upon this approach (Box 14.2). 

Radiotherapy followed by combination chemotherapy is recommended for patients with symptomatic brain metastases. Dexamethasone and anticonvulsants are also administered for symptom control and seizure prevention, respectively. 

Malignant mesothelioma, described more than 100 years ago, is a comparatively rare tumor that occurs in the pleura and peritoneum, membranes that surround the lungs, line the thoracic cavity, surround the gut, and line the abdominal cavity. The survival time of mesothelioma patients is often less than a year, in spite of chemotherapy and radiotherapy. Combined therapy and surgical resection in cases of early diagnosis, a treatment currently being tested, has produced a few long-term (more than five years) survivors (Ant-man, et ah, 1980 Antman et ah, 1983), usually in cases with peritoneal rather than pleural involvement. 

The MACH-NC study included a subset analysis of six randomized trials of 861 patients evaluating neoadjuvant with or without adjuvant chemotherapy combined with radiotherapy vs concomitant/alternating chemotherapy. No significant benefit was associated with adjuvant or neoadjuvant chemotherapy. A trend in favor of concomitant or alternating chemoradiotherapy was found but was not determined to be statistically significant (p =... 

Fu KK, Phillips TL, Silverberg IJ, et al. Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced inoperable head and neck cancer update of a Northern California Oncology Group randomized trial. J Clin Oncol 1987 5 1410-1418. 

Additionally, MMPIs are not expected to replace currently used, proven-effective modalities of cancer treatment such as radiotherapy, hormonal/chemotherapy, or surgery. It is predicted that they will be clinically developed for use in combination with these agents. As expected, given nonoverlapping toxicities and differing mechanisms of action, MMPIs have been combined preclinically with radiation therapy (4), cytotoxic (5-9), resultant additive or supraadditive efficacy. With these data in mind, the ability to combine an MMPI with radiation therapy, chemotherapy, and hormonal therapy may become an important feature in the ultimate clinical success of these agents. 

Small cell lung cancer (SCLC) includes approximately 20-25% of all cases of lung cancer seen worldwide. SCLC differs from other types of lung cancer in its more aggressive course and its superior responsiveness to chemotherapy and radiotherapy. The main modality of treatment for SCLC is combination chemotherapy. Eor patients with limited disease achieving a major response on chemotherapy, this is usually combined with concurrent thoracic irradiation. Prophylactic whole brain irradiation is often administered to complete responders because of the high probability of CNS relapse with associated morbidity. 

Combination chemotherapy administered concurrent with radiation has produced the most promising results in advanced, unresectable disease. The important study of Merlano et al. randomized 157 patients to conventional radiotherapy vs. cisplatin/5-FU given concurrent with radiation in alternating weekly fashion. They reported a 3-year survival rate of 41% with concurrent therapy vs. 23% with radiation alone (p < 0.05) and 5-year survival rate of 24% vs. 10% (p < 0.02) [136]. Taylor et al. reported significantly improved disease-free survival rates in patients treated with concomitant cis-platin/5-FU and radiation over sequential therapy (17 months vs. 13 months, p = 0.003) in their study of 214 patients with unresectable disease [137]. 

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