Pretreatment biopsies in 54 patients with Stage II and 37 patients with Stage III squamous cell carcinoma of the uterine cervix were reviewed. The patients were all diagnosed, staged, and treated in a uniform manner in a single radiation therapy unit. The biopsies were scored for degree of keratinization, nuclear pleomorphism, frequency of mitoses, cell size, inflammation, desmoplastic pattern of invasion, and presence or absence of vascular infiltration by tumor. Regression analysis and comparative survivals were analyzed to identify histologic parameters of prognostic value. The 5-year survivals were 60 and 32% for Stage II and III tumors, respectively. None of the histologic parameters evaluated was found to predict patient survival. Subclassification of the tumors by World Health Organization grading criteria also failed to predict patient survival. Stage of disease was the only factor that correlated with patient outcome.
AbstractStandard chemotherapeutic regimens, such as cisplatin and etoposide, may improve quality of life and prolong survival in patients with incurable non-small cell lung cancer (NSCLC). This trial was designed to evaluate the activity and toxicity of a regimen combining three of the most active agents against advanced-stage NSCLC: mitomycin C, etoposide, and cisplatin (MEP). Sixty-eight patients with stage IIIB (pleural effusion) or IV NSCLC received cisplatin 80 mg/m2 i.v. on day 1 and etoposide 80 mg/m2 i.v. on days 1, 2, and 3 every 3 weeks along with mitomycin C 10 mg/m2 i.v. on day 1 of the first and third cycles for a median of four cycles (range, 1–11). Median age was 59 years, and nine patients were enrolled after relapse from previously treated early-stage NSCLC. Eighty-eight percent of patients had stage IV disease, and 14 (21%) had brain metastases at diagnosis. Palliative radiotherapy was given to 10 patients (15%) before MEP and to 17 (25%) concurrent with MEP. The major toxicity of MEP was myelosuppression, with grade 3–4 neutropenia in 74% of patients. Sixteen patients (24%) had documented infections, and there were eight (12%) treatment-related deaths. Partial response was observed in 24 patients (35%) with a median duration of 4.4 months, (range 1.4–13 months). Median survival was 8.1 months (range, 1–34 months), and 1-year survival was 32%. The addition of mitomycin C to cisplatin and etoposide resulted in response and survival rates comparable with those achieved with standard regimens in patients with advanced NSCLC but was associated with substantial hematologic toxicity and unacceptable treatment-related mortality.
In a series of three consecutive pilot studies conducted between 1977 and 1982 at Wayne State University, Detroit, Michigan, 191 consecutive patients with previously untreated, locally advanced head and neck cancer were treated with cisplatin (CDDP), vincristine, and bleomycin or CDDP and 5-fluorouracil (5-FU) infusion before definite surgery or radiation. A 39% (75/191) rate of complete clinical responses was achieved. Thirty-two of the chemotherapy-induced complete responders underwent radical surgery. Thirteen had no histologic evidence of residual disease in the surgically resected specimen. The CDDP and 5-FU infusion combination achieved the highest histologic complete response rate. All histologically complete responders who had completed local radiation therapy are clinically free of disease at median follow-up of 36 months. Patients who achieved complete response both clinically and histologically had superior survival as compared to patients who achieved complete response clinically and were subsequently found to have residual tumor in their surgically resected specimen (P = 0.01). An analysis of the clinical and pathological pretreatment characteristics was performed to identify factors predictive of histologic complete response. Advanced nodal disease correlated inversely with the achievement of negative histology in the surgically resected specimen (P = 0.02). No other factors were significant in predicting response. Cancer 59:233–238, 1987.
One-hundred fourteen patients with advanced testicular cancer were randomized to treatment consisting of either high-dose (120 mg/m2, monthly) or low-dose (15 mg/m2, daily X 5 monthly) cisplatin, both combined with vinblastine and bleomycin. There were 60 (53%) complete remissions and 42 partial remissions for an overall response rate of 90%. An additional 11 patients, 4 with carcinoma and 7 with mature teratoma, following surgical cytoreduction, were rendered free of disease. There was a significantly higher complete response rate for high dose induction chemotherapy, 63%, when compared with low dose, 43% (P = 0.03). A survival advantage was also observed for patients receiving high-dose therapy (P = 0.009). For the subgroup of patients with maximal disease and embryonal ± teratoma ± seminoma histology there was a clear advantage in favor of high-dose over low-dose therapy both in complete response rate and survival (P = 0.03). There have been only four relapses, all occurring within 1 year of study entry. While there has been a higher frequency of leukopenia, renal, neuromuscular, and mucosal toxicity with high-dose therapy, thus far no irreversable toxicity leading to functional impairment has been seen. The authors have demonstrated a clear-cut relationship for dose of therapy, not only with response and survival, but with the increased potential for cure as well. Cancer 53:1029-1035, 1984.
Seventy-seven patients with squamous cell carcinoma of the oropharynx were treated by preoperative radiation therapy (4000-5000 rad) followed by surgical resection. The original biopsy specimens were evaluated for degree of keratinization, nuclear pleomorphism, frequency of mitoses, inflammatory response, vascular invasion, and pattern of invasion. Multivariant analysis (Cox regression model) and life table survival function were used to determine the relative contributions of the clinical and histologic parameters to patient outcome. The results were as follows: (1) large tumor size, nodal metastases, and male sex were found to be predictive of a poorer survival (P = 0.004, 0.0167, and 0.0237, respectively); and (2) an analysis of a combination of clinical and histologic parameters demonstrated that the pattern of invasion was the only histologic factor that was predictive of survival (P = 0.0436). Neoplasms invading as large cohesive aggregates indicated a better prognosis than neoplasms invading as thin, irregular cords or individual cells. Restricting the statistical evaluation to only histologic factors (excluding clinical factors) demonstrated that increased frequency of mitoses also correlated with poor survival (P = 0.0218). Further restriction of the analysis to T2 and T3 neoplasms that have similar survival times indicated that both frequency of mitoses and pattern of invasion were of prognostic value in predicting survival (P = 0.0127 and 0.0168, respectively).
Sixty-one assessable patients with advanced small cell and non-small cell carcinoma of the lung were given PCNU on an intermittent every 6-week schedule. Starting doses ranged from 75 mg/m2 for poor-risk patients to 100 mg/m2 for good-risk patients, depending on the bone marrow, liver, and renal status. Six partial responses (two small cell carcinoma, two adenocarcinoma, two large cell carcinoma) of short duration were documented. The major toxic effects were thrombocytopenia (35%) and leukopenia (16%). PCNU does not appear to have sufficient antitumor activity to warrant further investigation in advanced lung cancer.
A prospective randomized trial was conducted at Wayne State University, Detroit, Michigan, to compare the efficacy of the combination of high-dose cis-diamminodichloroplatinum, Oncovin (vincristine) and bleomycin (COB) to that of weekly methotrexate (MTX) in the induction and maintenance of remission in patients with previously treated advanced squamous cell carcinoma of the head and neck. Complete response (CR) was observed in 11.1% of patients treated with COB and in 8.3% of patients treated with weekly methotrexate. The overall response rate (PR + CR) was 33.3% to methotrexate versus 40.7% to COB. This difference was not significant, nor was the survival of patients treated by either modality. Important variables affecting survival in this study proved to be good performance status (greater than or equal to 70) and response to therapy. Nausea and vomiting were the more common side effects of COB (56%), while hematologic toxicity was more frequent and more severe in the methotrexate arm (75%). Combination chemotherapy with COB is not more effective in producing response or prolonging survival than weekly methotrexate in patients with advanced head and neck carcinoma when both regimens are compared in a randomized study.
