Christopher J. Williams

HISTOPATHOLOGY IN THE PREDICTION OF RELAPSE OF PATIENTS WITH STAGE I TESTICULAR TERATOMA TREATED BY ORCHIDECTOMY ALONE

259 patients with stage I non-seminomatous germ-cell testicular teratoma who were treated by orchidectomy alone and monitored at one often centres in the United Kingdom were followed for a median of 30 months. 62 of the 70 relapses occurred in the first 18 months after orchidectomy. The 2-year relapse-free rate was 74%, falling to 68% at 4 years. Histological sections from 233 of the orchidectomy specimens were reviewed centrally. Four features independently predicted relapses: invasion of testicular veins, invasion of testicular lymphatics, absence of yolk-sac elements, and presence of undifferentiated tumour. An index, based on the number of these features observed, identified a high-risk subgroup of 55 patients who had a 42% relapse-free rate at 2 years.

Cisplatin combination chemotherapy versus chlorambucil in advanced ovarian carcinoma: mature results of a randomized trial.

A randomized study to compare the efficacy of combination chemotherapy (cisplatin, doxorubicin, cyclophosphamide: PACe) with chlorambucil (CB) in International Federation of Gynecology and Obstetrics (FIGO) stage III and IV ovarian carcinoma was conducted between May 1979 and October 1983. Patients failing initial CB were subsequently eligible for treatment with PACe. Eighty-nine patients were randomized and 85 were eligible for analysis; as of date, 72 of these patients have died. The majority of patients in this study had bulky residual disease after their initial laparotomy (76%). Complete response (CR) was documented by a second laparotomy after five cycles of combination therapy or 6 to 12 months alkylating agent therapy. The overall response rate (CR plus partial response [PR]) for the combination (PACe, 68%) was significantly higher (P = .0004) than that for the chlorambucil (CB, 26%). However, the median survival was not improved (PACe, 13 months; CB, 11 months) and the survival curves were not significantly different (log rank test P = .25). The results of this study are comparable to preliminary data reported from other similar randomized studies. PACe, as administered in this study, is not indicated as routine therapy in patients with bulky residual ovarian carcinoma.

A phase II study of tamoxifen in ovarian cancer

A phase II study of tamoxifen was conducted in 22 patients with stage III and IV ovarian cancer who had failed chemotherapy and who had evaluable disease. Tamoxifen was administered at a dose of 20 mg twice daily continuously until evidence of progression. Twenty-one patients had progression of disease within 3 months and one patient had stable disease for 6 months. There were no objective responses to this treatment.

Surgery after initial chemotherapy for localized small-cell carcinoma of the lung.

Despite the high response rates induced by chemotherapy, many patients with limited small-cell lung cancer (SCLC) relapse at the site of primary disease. Failure of radiotherapy to overcome this has led to the use of surgery as part of a combined modality approach. Between December 1981 and December 1985, 189 patients with SCLC were assessed for suitability for surgery after an initial three cycles of chemotherapy (doxorubicin, cyclophosphamide, and etoposide). Fifty-seven were found to have limited disease, and of these, 19 were ineligible or unfit for surgery. Of the 38 eligible patients, 84% had an objective response to three cycles of chemotherapy and 25 were deemed suitable for surgery after restaging. At thoracotomy, four were inoperable, nine had a lobectomy, and 12 had a pneumonectomy. There was no evidence of viable SCLC in four resection specimens (one stage 1, two stage 2, one stage 3 at presentation), no viable SCLC but an entirely separate focus of viable poorly differentiated squamous carcinoma (SqLC) in one, and the remaining specimens contained viable SCLC. Survival of patients selected to undergo tumor resection was excellent (median survival, 33 months; plateau phase, 48% alive at 3 to 5 years), but survival of the entire group with limited SCLC was not dissimilar from that reported in previous series of limited-stage tumor treated with chemotherapy alone. Long-term survival appeared to be largely restricted to those with no evidence of viable SCLC at surgery (no viable SCLC, zero of five relapsed; viable SCLC, 13 of 16 relapsed and/or died). This prospective study confirms the feasibility of the combined modality approach, but suggests that any improvement in overall survival is likely to be small. Until the results from multicenter randomized trials are available, surgery, as part of a combined modality program, should be regarded as experimental.

Involvement of the gastrointestinal tract by metastases from germ cell tumors of the testis

Six cases of metastatic germ cell tumors of the testis involving the gastrointestinal (GI) tract are reported. Three cases were primary seminomas, and three were nonseminomatous. All six cases involved the upper GI tract, three occurring at presentation and three at relapse, with a disease‐free interval of 3 months to 10 years. Isolated GI involvement did not occur. The presumed mode of spread was by haematogenous dissemination in three and direct extension from paraaortic lymph nodes in three. Symptoms suggestive of involvement were severe abdominal pain secondary to high intestinal obstruction or mucosal ulceration, severe lumbar pain, and symptoms of anemia as a result of clinically evident or occult blood loss. Four patients were now disease‐free after chemotherapy, one died of an unrelated illness, and one patient was receiving treatment for relapsing disease.

Clinical features and management of malignant histiocytosis of the intestine

This article documents the clinical course of nine patients diagnosed as having malignant histiocytosis of the intestine (MHI). Five patients had a history of gluten‐sensitive enteropathy. This tumor commonly affects the small bowel in a widespread, patchy fashion causing ulceration, stricture formation, and perforation. Metastases to mesenteric nodes, liver, and the bone marrow were common. Although the diagnosis of MHI was often made at laparotomy, surgical resection, even when extensive, was not curative in any case. All nine patients were treated with a variety of chemotherapeutic regimes. This tumor proved chemosensitive, although response was usually brief and difficult to accurately evaluate. Chemotherapy was poorly tolerated because these patients were malnourished. In two cases small bowel perforation occurred, and in one gastrointestinal bleeding occurred after chemotherapy. Eight patients have died of disease from 0 to 16 months after the diagnosis was made, and a single patient is apparently cured 5+ years after completing chemotherapy. Malignant histiocytosis of the intestine has a characteristic clinical course. It is hoped that increased clinical awareness and early diagnosis will improve the outcome.

A multicenter, randomized trial of flat dosing versus intrapatient dose escalation of single-agent carboplatin as first-line chemotherapy for advanced ovarian cancer: an SGCTG (SCOTROC 4) and ANZGOG study on behalf of GCIG

BACKGROUNDnThe aim of the study is to demonstrate that intrapatient dose escalation of carboplatin would improve the outcome in ovarian cancer compared with flat dosing.nnnPATIENTS AND METHODSnPatients with untreated stage IC-IV ovarian cancer received six cycles of carboplatin area under the curve 6 (AUC 6) 3 weekly either with no dose modification except for toxicity (Arm A) or with dose escalations in cycles 2-6 based on nadir neutrophil and platelet counts (Arm B). The primary end-point was progression-free survival (PFS).nnnRESULTSnNine hundred and sixty-four patients were recruited from 71 centers. Dose escalation was achieved in 77% of patients who had ≥1 cycle. The median AUCs (cycle 2-6) received were 6.0 (Arm A) and 7.2 (Arm B) (P < 0.001). Grade 3/4 non-hematological toxicity was higher in Arm B (31% versus 22% P = 0.001). The median PFS was 12.1 months in Arm A and B [hazard ratio (HR) 0.99; 95% confidence interval (CI) 0.85-1.15; P = 0.93]. The median overall survival (OS) was 34.1 and 30.7 months in Arms A and B, respectively (HR 0.98; 95% CI 0.81-1.18, P = 0.82). In multivariate analysis, baseline neutrophil (P < 0.001), baseline platelet counts (P < 0.001) and the difference between white blood cell (WBC) and neutrophil count (P = 0.009) had a significant adverse prognostic value.nnnCONCLUSIONSnIntrapatient dose escalation of carboplatin based on nadir blood counts is feasible and safe. However, it provided no improvement in PFS or OS compared with flat dosing. Baseline neutrophils over-ride nadir counts in prognostic significance. These data may have wider implications particularly in respect of the management of chemotherapy-induced neutropenia.

A phase II study of ifosfamide and cisplatin chemotherapy for metastatic or relapsed carcinoma of the cervix

SummaryA total of 44 women received a combination of ifosfamide (1.5 g/m2 daily x5) and cisplatin (50 mg/m2 on day 1 only) as first-line chemotherapy for recurrent or metastatic carcinoma of the cervix. In all, 12/42 (38%) evaluable patients responded, with the median duration of response being 7 months. Bone marrow and gastrointestinal toxicity were frequently severe. There were 3 septic death. Although cisplatin plus ifosfamide is an active combination against this disease, these results suggest that it is no more so than either drug used alone.

ChlVPP chemotherapy in advanced Hodgkin's disease

Between March 1978 and January 1987 54 patients with advanced Hodgkins disease (HD) or relapse following radiotherapy (RT) for Hodgkins disease have been treated with combination chemotherapy consisting of chlorambucil, vinblastine, procarbazine and prednisolone (ChlVPP). A subgroup of five patients with bulky mediastinal disease received mantle RT in addition to ChlVPP chemotherapy. Forty-two patients (77.8%) entered complete remission with 33 (61.0%) remaining in unmaintained remission and 44 (81.5%) alive at a median follow up of 51 months (range: 22-103). The treatment was generally well tolerated with minimal toxicity. ChlVPP is effective first-line treatment for Hodgkins disease with results which may be comparable to those achieved for MOPP but with significantly less toxicity.

Extensive stage small cell carcinoma of the bronchus

SummaryFifty-four patients whose disease had been staged as extensive small cell carcinoma of the bronchus were randomised to receive either CAV1 (cyclophosphamide 600 mg m-2 i.v., adriamycin 50 mg m-2 i.v., given on day 1, and etoposide 500 mg m-2 p.o. given on day 3) or CAV5 (cyclophosphamide and adriamycin given as for CAV1, etoposide 500 mg m-2 given in divided dose over days 3–7) on a 21-day schedule. The two regimens proved comparable (CR+PR 55% vs 56%), and the survival curves were virtually superimposable (median survival: CAV1, 8 months; CAV5, 9 months). Only five patients are still alive. The toxicity of the two treatments was similar. The scheduling of etoposide over 1 or 5 days seemed clinically unimportant in this study, perhaps because of concurrent use of other effective chemotherapy drugs.