Martin D. Goodman

Hyperthermic intraperitoneal chemotherapy in ovarian cancer: first report of the HYPER-O registry.

Introduction: An analysis of experience of surgical and gynecologic oncologists in the United States with the use of hyperthermic intraperitoneal chemotherapy for women with invasive epithelial ovarian cancer (EOC). Methods: An Internet-based registry (HYPER-O) collected data from collaborating institutions. Eligibility included women with EOC treated with hyperthermic intraperitoneal chemotherapy. Borderline and nonepithelial cancers were excluded. Results: As of July 1, 2008, 141 women were eligible for analysis treated at the following time points: frontline (n = 26), interval debulking (n = 19), consolidation (n = 12), and recurrence (n = 83). The mean perfusion temperatures were 38.5 to 43.6°C (median, 41.9°C) for inflow and 36.9 to 42.9°C (median, 41°C) for outflow for 30 to 120 minutes. Treatment was with a platinum agent (n = 72), mitomycin (n = 53), or a combination (n = 14). Median follow-up was 18 months (range, 0.3-140.5 months) and median overall survival 30.3 months (95% confidence interval, 23.0-37.6) with 2-, 5-, and 10-year overall survival probabilities of 49.1%, 25.4%, and 14.3%, respectively. Of the 141 patients, 110 (78%) experienced recurrence of ovarian cancer and 87 died, 3 (0.5%) dying within 30 days of surgery. In the multivariable analysis, the factors significant for increased survival were sensitivity to platinum response (P = 0.048), completeness of cytoreduction scores of 1 or 0 (P = 0.025), carboplatin alone or a combination of 2 or more chemotherapy agents used (P = 0.011), and duration of hospital stays of 10 days or less (P = 0.021). Conclusions: Hyperthermic intraperitoneal chemotherapy is a viable additional treatment option for patients with invasive EOC and may extend life in selected groups. It warrants further study in randomized controlled trials.

The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with Mitomycin C versus Oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are gaining acceptance as treatment for selected patients with colorectal cancer with peritoneal carcinomatosis (CRCPC). Tremendous variations exist in the HIPEC delivery.

Chemotherapy for intraperitoneal use: a review of hyperthermic intraperitoneal chemotherapy and early post-operative intraperitoneal chemotherapy

Peritoneal spread of tumors is a major problem in cancer management. Patients develop a marked deterioration in quality of life and shortened survival. This is in part due to bowel obstructions, marked ascites, and overall increase debilitation. Standard medical management has shown to be inadequate for the treatment of these problems. Surgery can palliate symptoms, however, it is unable to be complete at the microscopic level by a significant spillage of tumor cells throughout the abdomen. Chemotherapy can have some improvement in symptoms however it is short lived due to poor penetration into the peritoneal cavity. The role of intraperitoneal chemotherapy is to maximize tumor penetration and optimize cell death while minimizing systemic toxicity. Hyperthermic intraperitoneal chemotherapy (HIPEC) and early post-operative intraperitoneal chemotherapy (EPIC) are two treatment methods that serve this role and have been shown to improve survival. This review will discuss different chemotherapies used for both of these treatment options.

Adjuvant therapy for pancreatic cancer.

Survival for patients with pancreas cancer is correlated to stage. Only 20% of patients present with localized disease amenable to potentially curative resection but, despite resection, the 5-year survival rate for early stage patients remains less than 25%. Current accepted standard of care is adjuvant gemcitabine following curative resection but there have been no conclusions regarding the role or timing of adjuvant chemoradiation. Although systemic disease represents the major risk for failure following resection, there are patients who would benefit from adjuvant local therapy that remain difficult to identify at present. This year at 2014 ASCO Gastrointestinal Cancers Symposium, Cho at al. (Abstract #325) presented the results of adjuvant gemcitabine with the addition of docetaxel followed by 5-FU chemoradiation for patients with resected pancreatic cancer. Kumar et al. (Abstract #330) compared adjuvant chemoradiation to adjuvant chemotherapy. Lastly Heestand et al. (Abstract #176) used a novel way to look at different biomarkers in serum of patients in the RTOG 9407 study and evaluated the survival depending on the type of chemotherapy used. A lower serum CEA and CA 19-9 gave a better overall survival in all patients which has already been established. Low levels of matrix metalloproteinase-7 (MMP-7) predicted an overall survival benefit from adjuvant gemcitabine, but not from 5-FU.

New Developments in the Management of Borderline Resectable Pancreatic Cancer

The optimal management of borderline resectable pancreatic cancer remains unclear. Neoadjuvant chemoradiation remains the most common approach in the United States, while neoadjuvant chemotherapy alone is also widely utilized and has demonstrated efficacy but there has been no clear consensus about a regimen that would be most beneficial in this setting. We will discuss three abstracts that were presented in the 2013 ASCO Gastrointestinal Cancers Symposium in which various regimens were evaluated in the neoadjuvant setting.

Does OPTINAB strategy ("stop-and-go") work in treatment of advanced pancreatic cancer (APC) with nab-paclitaxel (nab) - gemcitabine (gem)?

e15672Background: MPACT study showed survival benefit of nab-gem vs. gem in APC [Von Hoff D, NEJM 2013]. Sensory peripheral neuropathy is a dose-limiting toxicity associated with nab. Neuromodulato...

Immunotherapy of Pancreatic Cancer

Pancreatic cancer is highly aggressive and notoriously difficult to treat. Unfortunately, the vast majority of patients are diagnosed at an advanced stage of the cancer, and only a small population is potentially curative by surgical resection. Although gemcitabine-based chemotherapy is typically offered as standard of care, most patients do not survive longer than 6 months. FOLFIRINOX has shown superiority over gemcitabine monotherapy in metastatic disease, but this regimen is optimal only for selective patients. Therefore, new therapeutic approaches are urgently needed. Pancreatic cancer cells that develop gemcitabine resistance would still be suitable targets for immunotherapy. Therefore, one promising treatment approach may be immunotherapy that is designed to target pancreatic-cancer-associated antigens. The identification of key signaling pathways involved in immune-system regulation, along with the development of early pancreatic tumors in mouse models have provided new opportunities for pancreatic cancer treatment and prevention. Immunotherapy for pancreatic cancer is a therapeutic approach that is designed to target pancreatic-cancer-associated antigens and regulatory signaling molecules. This approach is currently at a crucial crossroad, and has entered clinical trials both as monotherapy and in combination with chemotherapy. It is hoped that the evolution of immunotherapy will offer a more optimistic prognosis for patients with pancreatic cancer.

Adjuvant Treatment for Pancreatic Cancer

Pancreatic cancer is the fourth leading cause of cancer deaths in both men and women. Surgical resection has been shown to be the only curable treatment available. Unfortunately only 20% of all patients diagnosed with pancreatic cancer are surgical candidates due to the aggressive biology of this disease. There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. The survival of these patients, even status post resection and adjuvant therapy, remains poor and therefore the need for alternative adjuvant therapies is needed. We will therefore discuss Abstracts #4124, #TPS4162, #4120 and #E15191 in this paper which are relevant to the issues described above.