Jaffer A. Ajani, MD

Jaffer A. Ajani, MD, spoke about the recent approvals of nivolumab plus ipilimumab and nivolumab plus chemotherapy for patients with esophageal squamous cell carcinoma.

Esophageal, gastroesophageal junction, and gastric cancers are underpublicized but are frequently lethal, and gastroesophageal junction adenocarcinomas are increasingly common diseases in the United States and around the world. Although often grouped together in studies of chemotherapy, clear distinctions can be made in the locoregional therapy of these diseases. Esophageal squamous cell carcinomas may be treated with surgery or radiation with concurrent chemotherapy, whereas esophageal adenocarcinomas and gastroesophageal junction adenocarcinomas are often treated with all three treatment modalities. Over the past several years, it has become increasingly evident that gastric cancer is a disease that is potentially sensitive to chemotherapy. In the perioperative setting—at least in the Western world—chemotherapy and sometimes radiation are applied. However, the optimal chemotherapy for advanced gastric or esophageal cancer remains unsettled, and there is no single standard regimen. Several new chemotherapy agents have demonstrated activity in these diseases, but the best chemotherapy remains to be determined. This paper will review the role of chemotherapy in gastroesophageal cancers.

Despite an overall rise in the incidence of gastrointestinal malignancies in the United States, there has been a significant decrease in the incidence of adenocarcinoma of the stomach over the past few decades. Nevertheless, gastric carcinoma remains the eighth leading cause of cancer death in the United States [1].

Carcinoma of the esophagus or the gastroesophageal junction is uncommon, accounting for approximately 1% of all malignancies in the United States [1]. An estimated 12,100 new cases and 10,900 deaths will occur in 1995.

Neuroendocrine tumors manifest in the gastrointestinal tract mainly as carcinoid and pancreatic islet-cell tumors. They comprise an interesting group of rare neoplasms that are derived from neuroendocrine cells interspersed within the gastrointestinal system amd throughout the body. Neuroendocrine tumors are well known for producing various hormonal syndromes and for their indolent clinical course in most patients, although some of these tumors do not produce hormones of clinical significance. Patients may have symptoms for many years before the diagnosis is suspected and confirmed.

The 6th University of Texas M. D. Anderson Cancer Center Investigators’Workshop was held on July 16–20, 2003, in Amelia Island, Florida.The purpose of these annual workshops has been to review the latest data onnew agents, with a particular emphasis on the broadly used agent irinotecan(Camptosar), and also novel regimens or agents.

The 5th University of Texas M. D. Anderson Cancer Center Investigators’Workshop was held on July 24-28, 2002, in San Diego, California.The purpose of these annual workshops has been to review the latest data onnew agents, with a particular focus on the broadly used agent irinotecan (CPT-11,Camptosar).

Local-regional carcinoma of the esophagus is often diagnosed inadvanced stages because the diagnosis is established when symptomsare severe. The prognosis of patients with local-regional carcinoma ofthe esophagus continues to be grim. While preoperative chemoradiotherapyincreases the fraction of patients who achieve pathologiccomplete response, that percentage is approximately 25%. In an attemptto increase the number of patients with either no cancer in the surgicalspecimen or only microscopic cancer, we adopted a three-step strategy.The current study utilized up to two 6-week cycles of induction chemotherapywith irinotecan (CPT-11, Camptosar) and cisplatin as step 1.This was followed by concurrent radiotherapy and chemotherapy withcontinuous infusion fluorouracil (5-FU) and paclitaxel as step 2. Oncethe patients recovered from chemoradiotherapy, a preoperative evaluationwas performed and surgery was attempted. All patients signed aninformed consent prior to their participation on the study. A total of 43patients were enrolled. The baseline endoscopic ultrasonography revealedthat 36 patients had a T3 tumor, five patients had a T2 tumor, andtwo had a T1 tumor. Twenty-seven patients had node-positive cancer(N1). Thirty-nine (91%) of the 43 patients underwent surgery; all hadan R0 (curative) resection. A pathologic complete response was noted in12 of the 39 patients. In addition, 17 patients had only microscopic(< 10%) viable cancer in the specimen. Therefore, a significant pathologicresponse was seen in 29 (74%) of 39 taken to surgery or 29 (67%)of all 43 patients enrolled on the study. With a median follow up beyond25 months, 20 patients remain alive and 12 patients remain free ofcancer. Our preliminary data suggest that the proportion of patientswith significant pathologic response can be increased by using thethree-step strategy.

The 4th Investigators’ Workshop sponsored by The University of Texas M. D. Anderson Cancer Center was held on July 25-29, 2001, in Colorado Springs, Colorado. The purpose of these annual workshops has been to review the latest data on new agents, with a particular focus on the broadly used agent irinotecan (CPT-11, Camptosar).

Octreotide (Sandostatin), a somatostatin analog, has a wide range of uses in the management of cancer patients. It is a unique molecule that specifically binds to somatostatin receptor subtype 2. This property of activating the receptor can result in a multitude of physiologic actions (for example, inhibition of synthesis and release of peptides in endocrine and neoplastic cells, antiangiogenesis, antisecretory effect in the gastrointestinal mucosa, anticholecystokinin activity retarding gallbladder motility, and reduction in splanchnic blood flow). In addition, in vitro experiments confirm that octreotide has cytostatic activity against a variety of malignancies. Octreotide is now widely used in the treatment of hormonal syndromes that result from a variety of neuroendocrine and endocrine neoplasms. Its dramatic effect in controlling malignant carcinoid syndrome and hormone-induced diarrhea (for example, from gastrinoma and VIPoma) has been well documented. However, the chronic use of octreotide can result in steatorrhea and gallstone formation.

Docetaxel (Taxotere) has been successfully investigated in the therapy for advanced gastroesophageal tumors as both a single agent and in combination regimens. As a single agent, phase II study results demonstrate an overall response rate of 17% to 24%, with occasional complete responses in a disease in which complete responses are rare. These figures classify docetaxel among the most active agents for the disease.

The 4th Investigators’ Workshop sponsored by The University of Texas M. D. Anderson Cancer Center was held on July 25-29, 2001, in Colorado Springs, Colorado. The purpose of these annual workshops has been to review the latest data on new agents, with a particular focus on the broadly used agent irinotecan (CPT-11, Camptosar).

We conducted a phase II study to assess the response rate and toxicity profile of the irinotecan (CPT-11, Camptosar) plus cisplatin combination administered weekly to patients with at least one previous chemotherapy for advanced adenocarcinoma of the stomach or gastroesophageal junction. Patients with histologic proof of adenocarcinoma of the stomach or gastroesophageal junction with adequate liver, kidney, and bone marrow functions were treated with 50 mg/m² of irinotecan plus 30 mg/m² of cisplatin, both administered intravenously 1 day a week for 4 consecutive weeks, followed by a 2-week recovery period.

The Fourth Investigators’ Workshop sponsored by The University of Texas M. D. Anderson Cancer Center was held on July 25-29, 2001, in Colorado Springs, Colorado.

The purpose of the annual workshops sponsored by The Universityof Texas M. D. Anderson

The 3rd Investigators’ Workshop, sponsored by The University of Texas M. D. Anderson Cancer Center, included five separate scientific sessions. The topics covered were colorectal carcinoma, lung carcinoma, breast carcinoma, miscellaneous

The purpose of the annual investigators’ workshops sponsored by The University of Texas M. D. Anderson Cancer Center has been to review the latest data on new agents, with a particular focus on

A phase II study was conducted to assess the response rate and toxicity profile of the combination of irinotecan (CPT-11, Camptosar) and cisplatin (Platinol) administered weekly to patients with untreated advanced

Irinotecan (Camptosar) is an active chemotherapeutic agent for lung, gastric, esophageal, and colorectal cancers and a potent radiosensitizer. This phase I study was designed to assess the maximum tolerated dose of weekly

Irinotecan (Camptosar, CPT-11), a member of the camptothecin family, represents the most active camptothecin available for clinical use today. Irinotecan is a topoisomerase I inhibitor. Topoisomerase enzymes support the topologic structure of DNA, thus facilitating translation and transcription. The enzyme topoisomerase I plays a crucial role in the relegation of single-strand breaks and in relieving torsional DNA stress.[1,2] Irinotecan and other camptothecin analogs interfere in this process by stabilizing the topoisomerase I/DNA cleavable complex.[2] This process is not compatible with prolonged cell survival.

Chemotherapy for advanced gastric and gastroesophageal junction carcinomas remains suboptimal. Both irinotecan (Camptosar) and cisplatin (Platinol) are active against this group of malignancies. This article focuses

Gastric cancer is often advanced and unresectable at diagnosis. Even when a curative resection is possible, the 5-year survival rate for patients with T2 or higher tumors is less than 50%. Survival rates are even lower if lymph node metastases are present at surgery. Many phase III trials of adjuvant therapy have been conducted around the world during the past 4 decades, but their interpretation varies in the East and West. In the West, postoperative treatment modalities have not proven to be superior to postsurgical observation alone. Thus, at present, the routine use of postoperative therapy should be discouraged. In the Orient, however, routine use of postoperative chemotherapy and/or immunotherapy is common after a surgical procedure. Further investigations that correlate treatment response with molecular markers are needed. Improved clinical trial designs, including better preoperative staging, standardized surgical techniques, inclusion of adequate numbers of patients, and the continued use of a surgery-alone control group, are essential. In addition, the incorporation of newer active agents, radiotherapy, and new strategies, such as preoperative therapy and selection of patients based on tumor biology, would result in much-needed advances. Less toxic approaches with novel mechanisms of action, such as antiangiogenesis therapy, tumor vaccines, monoclonal antibodies, and matrix metalloproteinase inhibitors, also hold promise. [ONCOLOGY 13(11):1485-1494, 1999]

Although gastric carcinoma is an uncommon disease in North America, its incidence is alarmingly high in Asia, South America, Eastern Europe, and countries of the former Soviet Union. Screening for gastric carcinoma is performed only on a limited basis in Japan; in the rest of the world, therefore, patients often present with advanced disease at the time of diagnosis.

Advanced gastric carcinoma remains an incurable disease with a median survival of 6 to 9 months, and available therapeutic approaches are predominantly palliative. In small controlled trials, systemic chemotherapy has