Chemotherapy for esophageal cancer

Esophageal cancer is supposed to be more sensitive to chemotherapy compared to other gastrointestinal cancers. Since cisplatin (CDDP) was developed, it has become a key drug for combined chemotherapy. At present, the combination of CDDP and 5-fluorouracil (5-FU) is the standard regimen for the treatment of esophageal carcinoma. Nedaplatin (CDGP) and paclitaxel (TXL) have shown favorable results either as a single agent or in combination with CDDP. Comparisons of drug efficacy between these new regimens and CDDP/5-FU in more cases has yet to be carried out. However, since esophageal cancer can hardly be cured by definitive chemotherapy alone, chemotherapy plays an important role in the multimodality therapy for esophageal cancer. The results of definitive chemoradiotherapy for advanced esophageal cancer has recently improved. The efficacy of preoperative (neoadjuvant) chemoradiotherapy in terms of survival benefit still remains controversial according to a meta-analysis of large-scale, randomized controlled trials (RCTs) when compared with surgery alone. A RCT completed by the Japan Clinical Oncology Group (JCOG) demonstrated the prognostic benefit of postoperative adjuvant chemotherapy for disease-free survival in comparison to surgery alone. Another RCT by JCOG has been conducted to clarify whether preoperative or postoperative chemotherapy may have a prognostic benefit in patients who undergo an esophagectomy.     

Chemotherapy is effective for stage I gastric cancer in patients with synchronous esophageal cancer

Gastric Cancer - Diagnostic endoscopy occasionally shows synchronous early gastric cancer (EGC) and esophageal cancer (EC) in the same patient. The treatment plan for these comorbid cancers is...     

Chemotherapy of breast cancer

Carcinoma of the breast will prove fatal to over 37,000 women in the United States in 1983, despite attempts at early diagnosis. Hormonal manipulation, known to provide effective palliation for many years, can now be effectively aimed at receptor positive women who have a 50–70% chance of responding. Newer agents, such as tamoxifen and aminoglutethimide offer the benefits of older treatments with less morbidity. Investigations of drugs acting at the level of the central nervous system are ongoing. Single agent chemotherapy is clearly effective in causing tumor regression, but effective combination chemotherapy provides more responses and a longer duration of response. The most effective combination regimens at present contain doxorubicin. Pharmacologic studies at the cellular level can be expected to provide more effective combinations. The most effective way to combine hormonal and chemotherapeutic treatments is not known. In receptor positive women without life-threatening disease, beginning with hormonal treatment may be effective in providing palliation at low toxic cost without jeopardizing overall survival. New efforts to cure clinically manifest metastatic breast cancer may eschew palliation as a prime goal. Techniques of synchronizing and of stimulating breast cancer to increase its susceptibility to cytotoxic drugs are under investigation. Immunotherapy is not established as a beneficial modality in the treatment of breast cancer, although levamisole has led to suggestive benefit in small controlled trials. The use of chemotherapy, and possibly of some hormonal treatments in appropriate patients, as an adjuvant to surgery prolongs disease-free survival. This approach, using established chemotherapeutic and hormonal agents when the metastatic disease is subclinical, is consonant with abundant evidence from experimental systems and other human cancers that are curable. Expectation of curing human breast cancer will likely require aggressive action at the time when the total body tumor burden is at a minimum.     

Chemotherapy of pancreatic cancer

The incidence of pancreatic cancer has been increasing in recent years. In spite of advances in diagnosis with new imaging techniques, the disease is usually advanced by the time of diagnosis. In order to improve the poor prognosis of patients with pancreatic cancer the development of an effective chemotherapy is essential. However, a review of the literature reveals that relatively few drugs have been evaluated for anticancer activity in pancreatic cancer. Anti-cancer drugs whose effectiveness have been confirmed are 5-fluorouracil, mitomycin C, streptozotocin, and adriamycin. A relatively high rate of response using combinations of these drugs has been reported. In addition to these drugs, tegafur is widely used in Japan. Other drugs need further trials and adequate evaluation.     

Chemotherapy of oesophago-gastric cancer

Oesophageal and gastric cancers are common tumors that represent a number of challenges for oncologists, gastroenterologists and surgeons. The prognosis remains poor with the majority of patients presenting with advanced disease. Combined chemotherapy and radiotherapy has demonstrated a survival benefit in patients with loco-regional oesophageal cancer compared to radiotherapy alone. In an interim analysis we have observed a 62% response rate using a chemoradiation regimen based on protracted venous infusion of 5-fluorouracil and cisplatin combined with radiotherapy in patients with inoperable oesophageal cancer. Improved outcomes with loco-regional disease has rekindled interest in preoperative therapy. In a trial comparing preoperative chemoradiation to surgery alone in patients with operable oesophageal adenocarcinoma, survival was improved with multimodality treatment In addition, a study including both adeno- and squamous carcinomas demonstrated a trend towards improved survival. A complete pathological response to chemoradiation was associated with significantly improved survival. Gastric cancer is one of the most chemosensitive solid tumors of the gastrointestinal tract with the majority of patients being suitable for palliative chemotherapy. The ECF (epirubicin, cisplatin, protracted venous infusion 5-fluorouracil) regimen was developed in the Gastrointestinal unit of the Royal Marsden Hospital and first reported in 1991. In a prospective randomised trial including 274 patients ECF has been compared with the standard combination of 5-fluorouracil, adriamycin and methotrexate (FAMTX) in patients with previously untreated gastric cancer. Overall response rate, failure-free and overall survival were significantly improved with ECF. ECF also demonstrated improved quality of life and cost effectiveness when compared to the FAMTX regimen. ECF should now be regarded as the standard treatment for advanced oesophago-gastric cancer against which new therapies should be compared. In addition the Medical Research Council are conducting a trial randomising patients between surgery alone and perioperative chemotherapy using the ECF regimen in operable gastric cancer.     

Chemotherapy of breast cancer

Carcinoma of the breast will prove fatal to over 37,000 women in the United States in 1983, despite attempts at early diagnosis. Hormonal manipulation, known to provide effective palliation for many years, can now be effectively aimed at receptor positive women who have a 50-70% chance of responding. Newer agents, such as tamoxifen and aminoglutethimide offer the benefits of older treatments with less morbidity. Investigations of drugs acting at the level of the central nervous system are ongoing. Single agent chemotherapy is clearly effective in causing tumor regression, but effective combination chemotherapy provides more responses and a longer duration of response. The most effective combination regimens at present contain doxorubicin. Pharmacologic studies at the cellular level can be expected to provide more effective combinations. The most effective way to combine hormonal and chemotherapeutic treatments is not known. In receptor positive women without life-threatening disease, beginning with hormonal treatment may be effective in providing palliation at low toxic cost without jeopardizing overall survival. New efforts to cure clinically manifest metastatic breast cancer may eschew palliation as a prime goal. Techniques of synchronizing and of stimulating breast cancer to increase its susceptibility to cytotoxic drugs are under investigation. Immunotherapy is not established as a beneficial modality in the treatment of breast cancer, although levamisole has led to suggestive benefit in small controlled trials. The use of chemotherapy, and possibly of some hormonal treatments in appropriate patients, as an adjuvant to surgery prolongs disease-free survival. This approach, using established chemotherapeutic and hormonal agents when the metastatic disease is subclinical, is consonant with abundant evidence from experimental systems and other human cancers that are curable. Expectation of curing human breast cancer will likely require aggressive action at the time when the total body tumor burden is at a minimum.