Eastern Cooperative Oncology Group Pilot Research Articles

Large-field, external beam irradiation as a surgical adjuvant for node-positive colon carcinoma: an Eastern Cooperative Oncology Group Pilot Study (PA285).

The Eastern Cooperative Oncology Group (ECOG) PA-285 study was designed as a pilot study to evaluate the effect of large-field, external beam abdominal irradiation as an adjuvant treatment for resectable stage C1 to C2 colon cancer. Eligible patients received 45 Gy directed to the tumor bed and periaortic lymph nodes, as well as 30 Gy to the liver. Patients were followed up for time to recurrence and for survival. Fourteen patients were enrolled. One elected not to have radiation after surgery; one died of acute hepatic radiation toxicity after a major deviation from protocol. Of the 12 remaining patients, seven survived longer than 10 years for a survival rate of 58%. Other than the fatal hepatic toxicity, side effects from radiation were moderate and of short duration. One patient failed to complete therapy because of ascites, had two episodes of partial bowel obstruction (successfully treated conservatively), and subsequently survived more than 10 years. Two of three patients with stage C1 tumors, four of eight with C2 tumors, and one with a C3 tumor were long-term survivors. This study demonstrates the feasibility and acceptable toxicity of this adjuvant regimen. The numbers are too limited to evaluate survival, but all seven survivors have lived more than 10 years.

Phase II study of ifosfamide, carboplatin, and oral etoposide chemotherapy for extensive-disease small-cell lung cancer: An Eastern Cooperative Oncology Group pilot study

Phase II study of ifosfamide, carboplatin, and oral etoposide chemotherapy for extensive-disease small-cell lung cancer: An Eastern Cooperative Oncology Group pilot study

Concurrent radiation therapy and chemotherapy for locally unresectable squamous cell head and neck cancer: an Eastern Cooperative Oncology Group pilot study.

The feasibility and success of an intensive chemoradiotherapeutic protocol for patients with locally advanced, unresectable squamous cell head and neck cancer was tested in this limited-institution, Eastern Cooperative Oncology Group phase II pilot study. Between December 1987 and September 1989, 57 patients were entered onto this trial. The treatment protocol consisted of three courses of a 4-day continuous fluorouracil infusion, a single cisplatin bolus injection, and concurrent split-course radiotherapy. After 30 Gy of radiation and two chemotherapy courses, patients were evaluated for response and for the possibility of surgical resection. Fifty-five of 57 registered patients are assessable for toxicity and 52 are assessable for response and survival. Toxicity was significant, but tolerable, although there were three toxic deaths. A complete response to this treatment was ultimately achieved by 77% of patients. Twenty-four patients remain relapse-free. The projected Kaplan-Meier 4-year relapse-free survival rate is 45% and the overall survival rate is 49%. Median relapse-free and overall survival durations are 26 and 37 months, respectively. Of the 28 treatment failures, 79% were locoregional. Fourteen patients underwent surgery. Six remain relapse-free. This aggressive concurrent chemoradiotherapy protocol appears feasible within a cooperative group. Treatment results are promising and appear durable. A randomized phase III clinical trial is currently underway.

Cisplatin, carboplatin, and cyclophosphamide combination chemotherapy in advanced-stage ovarian carcinoma: an Eastern Cooperative Oncology Group pilot study.

Cyclophosphamide (CTX) 600 mg/m2, carboplatin 280 mg/m2, and cisplatin 50 mg/m2 were administered on day 1 every 4 weeks to 41 previously untreated ovarian cancer patients with residual disease greater than 2.0 cm after primary laparotomy. Of 22 patients with measurable disease treated with up to eight cycles of therapy, the overall clinical response rate was 73% (exact 95% confidence interval [CI], 50% to 89%), with 50% complete response (CR). Six of 11 clinical CR (cCR) patients underwent surgical restaging; three pathologic CRs (pCRs) and three pathologic partial responses (pPRs) with residual disease less than 2.0 cm were documented. Fourteen patients had nonmeasurable but assessable disease; the clinical response rate was 57% (Cl, 29% to 82%) with two (14%) CRs. Second-look surgery was performed in one of the two cCR patients; a pPR was documented. Five patients with nonassessable disease were stable during chemotherapy; two underwent surgery and had pCRs. The median time to treatment failure (TTF) was 14.8 months, and median survival for the 41 patients is 26.7 months. Overall, 37% of the patients had progression-free intervals of at least 2 years, and 27% have survival times in excess of 3 years. Hematologic toxicity was substantial but manageable, with 58% and 66% experiencing a granulocyte nadir less than 500/microL and a platelet nadir less than 50,000/microL, respectively. One treatment-associated fatality occurred as a result of leukopenic sepsis and renal failure in the setting of progressive disease and ureteral obstruction. Mild to moderate nausea and vomiting occurred in most patients, but none experienced severe ototoxicity or peripheral neuropathy. Over all courses, 73% of the projected dose intensity of CTX and carboplatin and 86% of cisplatin were delivered. Since granulocytopenia and thrombocytopenia were dose-limiting, the addition of colony-stimulating factors that support both myeloid and megakaryocyte precursors may permit further dose intensification.

A phase II evaluation of combination chemotherapy plus aminoglutethimide in women with metastatic or recurrent breast carcinoma. An Eastern Cooperative Oncology Group Pilot Study.

The Eastern Cooperative Oncology Group (ECOG) conducted a pilot study of combination chemotherapy with cyclophosphamide, doxorubicin, and 5-fluorouracil plus aminoglutethimide (250 mg three times daily with hydrocortisone supplementation of 40 mg daily) as primary therapy for estrogen receptor-positive or unknown advanced breast carcinoma to assess whether these agents can be safely combined and to provide a preliminary estimate of response rate. A total of 47 patients, 45 with metastatic breast cancer and two with stage IV disease who were rendered clinically disease free following surgical resection of chest wall recurrence, were treated. Leukopenia and mucositis were the most frequent toxicities requiring dose reduction, but only five patients (10.6%; 95% confidence interval, 1.8-18.4%) experienced life-threatening leukopenia (less than 1000/mm3) at some point during their therapy. Neurologic side effects attributed to aminoglutethimide, predominantly lethargy, were reported in less than one-third of patients, and rarely required dose reduction. One elderly patient developed clinical hypothyroidism during the first 3 months on therapy and experienced a cardiac arrest at home while receiving supplemental thyroid hormones. The overall complete plus partial response rate in 45 patients was 55.5% (95% confidence interval, 41-70%). Among 16 patients with measurable disease, the complete plus partial response rate was 75% (95% confidence interval, 54-96%). The complete plus partial response rate in 29 patients with nonmeasurable but evaluable disease was 45% (95% confidence interval, 27-63%) and an additional 14% had improvement in bone pain. Eight patients electively discontinued chemotherapy after 7-24 months of therapy, but continued aminoglutethimide. The median time to disease progression is 462 days (15.4 months); 25% of patients died by 552 days (18.4 months), and the median duration of survival is predicted to be 889 days (29.6 months). We conclude that aminoglutethimide can be combined with this doxorubicin-based regimen with acceptable toxicity and an overall response rate which is similar to that observed on prior ECOG trials with cyclophosphamide, doxorubicin, and 5-fluorouracil.

Phase II trial of PCNU in advanced malignant melanoma: an Eastern Cooperative Oncology Group pilot study

PCNU, a chloroethylnitrosourea with high alkylating activity, low carbamoylating activity, optimal octanol: water partition coefficient and broad activity in animal systems, was administered to 32 evaluable patients with measurable metastatic melanoma by brief intravenous infusions every six weeks. The initial dose was 75 or 100 mg/m2, with escalation or reduction for toxicity, and a total of 58 evaluable courses were given. Half of the patient population had received no prior chemotherapy. One objective complete response (duration 585 days) and four objective partial responses (durations 55, 169, 405 and 102 days) occurred, the last recorded in a patient previously treated with DTIC. These responses included visceral, nodal and subcutaneous disease. The response rate was 16% with a 95% confidence interval of 5.5 to 33.7%. Thrombocytopenia was dose-limiting and leukopenia was relatively mild. Gastrointestinal toxicity was less severe than expected for a nitrosourea. PCNU has comparable clinical activity to that of other nitrosoureas in patients with advanced melanoma.

Phase II trial of PCNU in advanced colorectal carcinoma. An Eastern Cooperative Oncology Group pilot study.

PCNU, a chloroethylnitrosourea with high alkylating activity, low carbamoylating activity, optimal octanol: water partition coefficient, and broad activity in animal systems was administered to 30 evaluable patients with measurable advanced colorectal carcinoma by brief intravenous infusions every 6 weeks. The initial dose was 75 or 100 mg/m2, with escalation or reduction for toxicity, and a total of 64 evaluable courses were given. Half of the patient population had received no prior chemotherapy. Two objective partial responses occurred. The response rate was 6.7% with a 95% confidence interval of 0.8-22.1%. Thrombocytopenia was dose-limited and leukopenia was relatively mild. Gastrointestinal toxicity was less severe than expected for clinically available nitrosoureas. In colorectal carcinoma, PCNU has limited clinical activity that does not appear to be superior to that of other nitrosoureas.

Total (half-body) systemic irradiation for occult metastases in non-small cell lung cancer: an Eastern Cooperative Oncology Group pilot report.

There is a high probability for patients with locally advanced, unresectable, nonmetastatic, nonsmall-cell bronchogenic carcinoma (NSCBC) to harbor subclinical distant metastases at diagnosis. Approximately 30% will disseminate in the first three months and an additional 50% will disseminate before a year has elapsed. Twenty advanced nonmetastatic patients with NSCBC were treated with localized split-course chest irradiation (LCI) plus total body body (upper and lower half-body) irradiation for occult metastases. Thirty equally advanced, nonmetastatic patients, who were treated with only localized split-course chest irradiation, were matched and served as a retrospective control group. The first 11 patients received HBI after LCI (Pilot Study No. 1), but five (45%) had evidence of distant metastases before UHBI was delivered. This was not different from the control group where 11 (37%) of the patients had evidence of distant dissemination less than 2 1/2 months from the onset of treatment. The remaining nine patients received UHBI first followed by LCI and LHBI (Pilot Study No. 2); only one (11%) had evidence of distant metastases in the first 2 1/2 months. Apparently, the median recurrence free survival, metastatic free interval, and median survival were significantly prolonged, and there was a decrease in the incidence of liver metastases in patients receiving HBI for occult metastases over the patients of the control group. An increase in local tumor control was seen when large single doses of UHBI were added to LCI. Although elective HBI seems to delay the appearance of distant metastases, it did not prevent their occurrence, alter patterns of first relapse, or significantly improve the overall survival. Nevertheless, a therapeutic gain may have been achieved and is discussed. These two high-risk Phase II Pilot Studies for the Eastern Cooperative Oncology Group (ECOG) have served as the basis for a larger randomized protocol where this therapeutic strategy will be tested against other therapies. The incidence of radiation pneumonitis with 800 rad of UHBI corrected for lung transmission was 9%, or one of 11 patients. A hypothesis and rationale for a more effective combined modality therapy in these patients is given.

Half-body and local chest irradiation as consolidation following response to standard induction chemotherapy for disseminated small cell lung cancer: an Eastern Cooperative Oncology Group pilot report.

Abstract A two-institution Phase 11 Pilot Study for the Eastern Cooperative Oncology Group (ECOG) used standard induction chemotherapy (cyclophosphamide and CCNU) followed by consolidation radiation therapy (RT) (600 rad of upper half-body irradiation plus 2000 rad in one week of localized chest irradiation) followed by maintenance chemotherapy in patients with extensive small cell bronchogenic carcinoma (SCBC). Nineteen patients were entered and 9 (47%) had partial responses (PR) after induction chemotherapy. No complete responses (CR) were seen. The 10 patients whose disease progressed were ineligible for consolidation RT and died with a short median survival time (MST) of 15 weeks. Of the 9 patients who were consolidated, 7(78%) had complete responses in the chest; five (63%) became overall complete responders. The MST of all consolidated responders was 44 weeks. At this writing, two of the 5 patients who achieved CR after RT consolidation were alive without disease for more than one year; another patient was alive with disease for almost one year. A control group consisting of patients with extensive SCBC was used for comparison; these patients were treated by the two participating institutions in an earlier ECOG protocol with the same chemotherapy regimen but without RT consolidation.