Tate Thigpen

Cis‐platinum in treatment of advanced or recurrent squamous cell carcinoma of the cervix: A phase ii study of the gynecologic oncology group

Thirty‐four patients with advanced or recurrent squamous cell carcinoma of the cervix no longer amenable to control with surgery and/or radiotherapy were treated with cis‐platinum 50 mg/m2 intravenously every three weeks. Among 22 patients who had received no prior chemotherapy, three complete and eight partial responses were observed (response rate 50%), whereas only two partial responses were observed among 12 patients who had received prior chemotherapy (response rate 17%). The observed response rate was marginally significantly higher among those with no prior chemotherapy (P = 0.059). The overall frequency of response was 38% (13/34). Responses were observed in those with pelvic (7/20) as well as extrapelvic disease (6/14). Adverse effects included primarily leukopenia (11/34), thrombocytopenia (13/34), nausea and vomiting (29/34), and azotemia (17/34). Adverse effects were generally mild to moderate and hence tolerable. Cis‐platinum thus appears to be a highly active agent in the treatment of squamous cell carcinoma of the cervix at the dose and schedule tested.

Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG)

The Gynecological Cancer Intergroup (GCIG) has previously reached consensus regarding the criteria that should be used in clinical trial protocols to define progression-free survival after first-line therapy as well as the criteria to define response to treatment in recurrent disease using the serum marker CA 125 and has specified the situations where these criteria should be used. However, the publications did not include detailed definitions, nor were they written to accommodate the new version of Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) now available. Thus, we recommend that the definitions described later in detail are incorporated into clinical trial protocols to maintain consistency. The criteria for defining progression are now acceptable in clinical trials of recurrent disease as they have since been validated (Pujade-Lauraine, personal communication, 2010). The GCIG requests that data from all clinical trials using these definitions are made available to GCIG trial centers so that continual validation and improvement can be accomplished. These definitions were developed from analyzing patients receiving cytotoxic chemotherapy and have not yet been validated in patients receiving molecular targeting agents.

Tamoxifen in the Treatment of Advanced or Recurrent Endometrial Carcinoma: A Gynecologic Oncology Group Study

PURPOSE In two large Gynecologic Oncology Group studies of patients with advanced or recurrent endometrial carcinoma and no previous systemic therapy, progestins have demonstrated activity against advanced or recurrent endometrial carcinoma with response rates between 15% and 25%. Tamoxifen has been reported as variously active or inactive with or without previous systemic therapy. The purpose of this study was to determine whether tamoxifen exhibits enough activity in patients with advanced or recurrent endometrial carcinoma, who have not received systemic therapy, to warrant a phase III trial. PATIENTS AND METHODS Sixty-eight eligible patients with advanced or recurrent endometrial carcinoma received oral tamoxifen 20 mg bid until toxicity was unacceptable or disease progressed. RESULTS Three complete (4%) and four partial (6%) responses were observed for an overall response rate of 10% (90% confidence interval [CI], 5.7% to 17.9%). Patients with tumors that were more anaplastic tended to respond less frequently. The median progression-free survival for all 68 eligible patients was 1.9 months (90% CI, 1.7 to 3.2 months). The median survival was 8.8 months (90% CI, 7.0 to 10.1 months). CONCLUSION Tamoxifen demonstrated modest activity at best against endometrial carcinoma and does not warrant further investigation as a single agent for this disease. Ongoing trials will assess the sequential use of tamoxifen and progestational agents.

Chemotherapy for advanced or recurrent gynecologic cancer

Studies of chemotherapy in advanced or recurrent gynecologic cancer have focussed on ovarian, cervical, and endometrial carcinoma. For celomic epithelial carcinomas of the ovary, a large number of cytotoxic agents have been shown to be active. Dramatic improvement in frequency of response with lesser improvement in survival has been noted with the use of cisplatin‐based combination chemotherapy as compared to single alkylating agents. More recent studies have evaluated alternative ways to employ cisplatin: higher dose schedules, intraperitoneal administration, and platinum compounds with a potentially better therapeutic index. None has yet been shown superior to a combination of relatively low‐dose cisplatin plus an alkylating agent with or without doxorubicin. Cisplatin remains the best studied and most active single agent in patients with squamous cell carcinoma of the cervix. While a number of other agents have demonstrated moderate activity, no combination of drugs has as yet proved superior to single‐agent cisplatin. In endometrial carcinoma, progestins and doxorubicin are the most active agents. Tamoxifen, cisplatin, and hexamethylmelamine appear to have moderate activity. No combination has yet been shown to be superior to single agents. Information on chemotherapy for less common gynecologic malignancies is largely anecdotal. Two observations are of note. Cisplatin‐based combination chemotherapy is highly active against germ‐cell neoplasms of the ovary. Cisplatin also has definite activity against mixed mesodermal sarcoma of the uterus.

Targeting the folate receptor: diagnostic and therapeutic approaches to personalize cancer treatments

BACKGROUND In cancer therapy, molecularly targeted agents have the potential to maximize antitumor efficacy while minimizing treatment-related toxicity. However, these agents may only be effective in specific tumor subtypes with defined genomic profiles. This emphasizes the importance of developing personalized cancer therapeutic strategies (i.e. through the use of companion diagnostic tests) to appropriately select and treat patients who are likely to benefit from specific targeted therapies, thus leading to improvements in clinical and safety outcomes. A potential biological target is the folate receptor (FR), which has been shown to be overexpressed on the surface of many cancers, including tumors of the lungs and ovaries. DESIGN We carried out a literature search to identify how the FR can be a potential target for selected tumors, and how the FR expression can be exploited by targeted therapies. RESULTS The two main therapeutic strategies for targeting the FR are based on the use of: (i) an anti-FR antibody (e.g. farletuzumab) and (ii) folate conjugates of folate-targeted chemotherapies and companion radiodiagnostic imaging agents (e.g. vintafolide and (99m)technetium-etarfolatide). Both of these strategies are being assessed in phase III trials. CONCLUSIONS The important role that the FR plays in cancer development and progression has led to the development of FR-targeted therapeutic approaches. To date, the promising data observed in phase II clinical trials have not been confirmed in phase III studies. Accordingly, there is a need for further research in the refinement of patient selection and identification of new therapeutic combinations. In particular, the development of these targeted therapies requires reliable methods to be developed to detect FR-positive tumors in order to help select patients who may benefit from treatment.

5 FU infusion with mitomycin‐C vs. 5 FU infusion with methyl‐CCNU in the treatment of advanced upper gastrointestinal cancer. A Southwest oncology group study

A randomized trial was conducted by the Southwest Oncology Group (SWOG) in advanced carcinoma of the stomach and pancreas. Patients were assigned to receive monthly 5‐fluorouracil 96‐hour continuous infusions with either bolus mitomycin‐C or oral methyl‐CCNU. Mitomycin‐C and methyl‐CCNU were administered every eight weeks. The 5 FU‐mitomycin combination produced a 14% and 22% response rate in disseminated stomach and pancreatic carcinoma, respectively. The combination of infusion 5 FU and methyl‐CCNU achieved responses in 9% and 5% of stomach and pancreatic tumors, respectively. There was ho significant difference in survival between limbs for either tumor. Median survival in gastric carcinoma on the 5 FU‐mitomycin regimen was 25 weeks vs. 18 weeks on the 5 FU‐methyl‐CCNU arm. In pancreatic carcinoma median survival on the mitomycin limb was 19 weeks as compared to 17 weeks on the methyl‐CCNU program. Leukopenia was greater for the first course on the mitomycin limb. Regression analysis demonstrated that performance status was the most important pretreatment characteristic for predicting survival in both tumors. Neither 5 FU infusion combination appears to significantly alter the dismal prognosis of advanced upper gastrointestinal neoplasms.

5FU infusion with mitomycin‐C versus 5FU infusion with methyl‐CCNU in the treatment of advanced colon cancer. A southwest oncology group study

The Southwest Oncology Group (SWOG) in a randomized trial evaluated 5FU infusions in combination with either Mitomycin‐C or Methyl‐CCNU in patients with disseminated large bowel cancer. A response rate of 18% was noted on the 5FU‐Mitomycin limb as compared to 16% on the Methyl‐CCNU arm (p = .39). Median survival for all treated patients was 43 weeks on both arms. Myelosuppression was found to be more significant on the Mitomycin‐C arm. Regression analysis demonstrated that performance status, sex, and primary site were significant pretreatment characteristics for predicting survival. The response rates associated with this burdensome method of 5FU administration in combination with either Mitomycin‐C or Methyl‐CCNU appear to offer little advantage over bolus 5FU alone.

Evaluation of bone scan as a screening work-up in primary and local-regional recurrence of breast cancer

To evaluate the use of radionuclide bone scan in staging patients with primary and local-regional recurrence of breast cancer, we reviewed the results in 265 patients with primary breast cancer who had the scan either preoperatively or within 6 weeks of surgery, and in 39 patients presenting with their first local-regional recurrence. All patients were clinically staged according to the revised 1983 criteria of the American Joint Committee for Cancer Staging and End-Results Reporting. None of the 92 with stage I and four of 95 patients with stage II had a positive scan. Eleven of 41 with stage IIIA and 13 of 37 with stage IIIB had a positive bone scan. In patients with their first local-regional recurrence, 12 of 39 had a positive scan. Follow-up scans were available in 61 patients with clinical stage I and II breast cancer who had adjuvant chemotherapy for pathological involvement of axillary node. There were six conversions observed in 61 scans obtained during the first year. Seven converted in follow-up scans in 47 patients in the second year. We conclude that although bone scans have a low positive yield in stage I and II breast cancer, their use in the preoperative setting and in the follow-up of patients with axillary node involvement detects early converters. Bone scans are justified in stage IIIA and IIIB breast cancer and in patients being evaluated for local-regional recurrence.

GIucose-6-Phosphate Dehydrogenase Jackson

A 66-year-old man presented with moderately severe hemolytic anemia. Hematologic and biochemical evaluation proved him to have a hitherto undescribed variant of erythrocyte glucose-6-phosphate dehydro