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PubMed1992

Ten-year outcome of patients with advanced epithelial ovarian carcinoma treated with cisplatin-based multimodality therapy.

PURPOSE: At the end of the 1970s it was thought that advanced epithelial ovarian cancer (EOC) could be cured by multimodality treatment using surgery, cisplatin-based combination chemotherapy, and radiotherapy (RT). Such multimodality treatment was used as standard therapy at our institution. Our long-term results are reviewed. PATIENTS AND METHODS: One hundred ninety-five previously untreated patients with stage III or IV EOC were treated between April 1979 and December 1982. All patients were to have debulking surgery, when feasible, followed by the administration of doxorubicin and cisplatin at 50 mg/m2 every 3 weeks until a total dose of doxorubicin of 450 mg/m2 had been reached. RT was used in addition in patients with disease remaining after the chemotherapy. Maintenance chemotherapy with oral cyclophosphamide and hexamethylmelamine (altretamine) was administered to patients who did not have a documented histologic complete remission. RESULTS: The 10-year overall and failure-free survivals were 4% and 8%, respectively. The median overall survival was 2 years. The achievement of a histologic complete response (n = 32) did not equate to cure because 20 (63%) of the patients eventually relapsed. Multivariate analysis identified residual disease of greater or less than 2 cm as the only independent prognostic factor. CONCLUSIONS: Our multimodality treatment program was noncurative for the majority of the patients. Innovative therapies are needed before we can hope to cure such disease.

Adult↗
PubMed2001

Recent advances in the treatment of epithelial ovarian cancer.

Ovarian cancer leads to more fatalities than any other form of gynaecological cancer in North America and Europe. Over the last 30 years survival figures have improved somewhat due to improvements in diagnosis, surgery and chemotherapy. Despite these advances, the majority of patients will die from their disease, with the overall 5-year survival being just 30%. The majority of patients with this disease will require treatment with cytotoxic chemotherapy. It is now well established that the platinum agents (cisplatin or carboplatin) are the most important drugs to be included in first-line regimens. More recently, randomised trials have confirmed the benefit of the addition of taxanes to platinum-containing regimens and the standard of care has become the combination of carboplatin and paclitaxel. Several unanswered questions remain regarding the optimal schedule, the optimum duration of treatment, possible benefits to be gained from the addition of other drugs and whether paclitaxel the best taxane. Despite high response rates to first line chemotherapy, the majority of patients with advanced ovarian cancer will relapse and will be candidates for further chemotherapy, which can palliate symptoms and improve survival even in recurrent disease. For a patient relapsing within six months of first-line treatment, studies have shown that there is little point in rechallenge with the same drugs. However, for patients who have a longer treatment-free interval the response rates to rechallenge with platinum is significant. A number of drugs have been shown to have activity in platinum- and taxane-refractory disease and are approved for this and/or other applications. These include topotecan, etoposide, pegylated liposomal doxorubicin, epirubicin, gemcitabine, altretamine, oxaliplatin and vinorelbine. Anti-oestrogens such as tamoxifen have a small but significant response rate. Recurrent ovarian cancer is a good setting to test investigational agents and compounds with promising activity including new platinums and taxoids, as well as a range of new compounds. Non-cytotoxic approaches that are showing promise include therapies designed to overcome drug resistance, signal transduction inhibitors, immunotherapy and gene therapy.

Drugs, Investigational↗
PubMed2005

Topotecan: weighing in when there are many options.

The manuscript by Armstrong et al. in this issue of The Oncologist, reviewing the toxicity and efficacy of full-dose topotecan delivered as second-line therapy in individuals with small cell lung cancer or ovarian cancer, will likely serve as both the most comprehensive and the final review of this active agent delivered at the U.S. Food and Drug Administration-approved dosage and schedule. The review represents large, relative lyhomogeneous patient populations with prior platinum exposure and convincingly describes topotecan as an agent with activity that is comparable with those of all other approved drugs in this setting and a well-defined and relatively circumscribed set of toxicities. While the activity of topotecan in small cell carcinoma provides individuals with the hope for further palliation at the time of tumor recurrence, as discussed by Dr. Markman in this issue, the best use of this agent in the management of recurrent ovarian cancer is far from clear because, in part, of a growing list of approved active agents, most notably liposomal doxorubicin, gemcitabine, and weekly paclitaxel; a return to platinum; or a host of other agents such as vinorelbine, altretamine, irinotecan, docetaxel, etoposide, and others. The most pressing need is to accept that palliative therapies are designed to palliate and improve symptoms, and to move away from end points of radiologic and marker response to a focus on "clinical benefit" and clinically more meaningful end points.

Antineoplastic Agents↗
PubMed1994

Paclitaxel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer.

Paclitaxel is a new anticancer agent with a novel mechanism of action. It promotes polymerisation of tubulin dimers to form microtubules and stabilises microtubules by preventing depolymerisation. In noncomparative trials, continuous infusion of paclitaxel 110 to 300 mg/m2 over 3 to 96 hours every 3 to 4 weeks produced a complete or partial response in 16 to 48% of patients with ovarian cancer and 25 to 61.5% of patients with metastatic breast cancer, many of whom were refractory to treatment with cisplatin or doxorubicin, respectively. 23 to 100% of patients with ovarian cancer achieved complete or partial responses with paclitaxel in combination with cisplatin, carboplatin, cyclophosphamide, altretamine and/or doxorubicin. Similarly, response rates of 30 to 100% were observed with paclitaxel plus doxorubicin, cisplatin, mitoxantrone and/or cyclophosphamide in patients with metastatic breast cancer. Comparative trials in patients with advanced ovarian cancer showed paclitaxel therapy to produce greater response rates than treatment with parenteral hydroxyurea (71 vs 0%) or cyclophosphamide (when both agents were combined with cisplatin) [79 vs 63%]. Paclitaxel was also more effective than mitomycin in 50 patients with previously untreated breast cancer (partial response in 20 vs 4% of patients). Paclitaxel therapy also produced promising results in patients with advanced squamous cell carcinoma of the head and neck, malignant melanoma, advanced non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), germ cell cancer, urothelial cancer, oesophageal cancer, non-Hodgkin's lymphoma or multiple myeloma, and was successfully combined with cisplatin, carboplatin and/or etoposide in patients with NSCLC, SCLC or advanced squamous cell carcinoma of the head and neck. Hypersensitivity reactions were initially a concern with administration of paclitaxel, although current dosage regimens have reduced the incidence of these events to less than 5%. The major dose-limiting adverse effects of paclitaxel are leucopenia (neutropenia) and peripheral neuropathy. Other haematological toxicity was generally mild. Cardiac toxicity was reported in small numbers of patients and most patients developed total alopecia. Several aspects of paclitaxel use remain to be clarified, including the optimal treatment schedule and infusion time, confirmation of the tolerability profile and efficacy of combination regimens in an expanded range of malignancies. Long term follow-up of paclitaxel recipients will also allow the effects of the drug on patient survival to be determined. Nevertheless, paclitaxel is a promising addition to the current therapies available, with significant activity reported in patients with advanced ovarian or breast cancer or other types of tumors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2001

A rapid and systematic review of the clinical effectiveness and cost-effectiveness of topotecan for ovarian cancer.

BACKGROUND: Ovarian cancer is the most common gynaecological cancer with an annual incidence of 21.6 per 100,000 in England and Wales. Due to the often asymptomatic nature of the early stages of the disease, most cases are not detected until the advanced stages. Consequently, the prognosis after diagnosis is poor and the 5-year survival rate in the UK is only about 30%. Current recommendations suggest that first-line chemotherapy for ovarian cancer should involve paclitaxel and platinum (Pt)-based therapy (cisplatin/ carboplatin), however, most patients develop resistant or refractory disease and require second-line therapy. Patients may respond to re-challenge with Pt-agents if the treatment-free interval is > 6 months, but an alternative is often required. Topotecan is one of six drugs currently licensed in the UK for second-line therapy, and recent reviews suggest that it has modest efficacy in the treatment of advanced disease and performs favourably against paclitaxel. However, these reviews are based on a limited number of reports mainly consisting of non-randomised Phase I and II studies. OBJECTIVES OF THE REVIEW: To examine the clinical effectiveness and cost-effectiveness of oral and intravenous topotecan (Hycamtin, SmithKline Beecham, UK) for the treatment of all stages of ovarian cancer. METHODS SEARCH STRATEGY: Sixteen electronic databases from inception to September 2000 and Internet resources were searched, in addition to the bibliographies of retrieved articles and submissions from pharmaceutical companies. METHODS INCLUSION AND EXCLUSION CRITERIA: Two reviewers independently screened all titles/abstracts and included/excluded studies based on full copies of manuscripts. Any disagreements were resolved through discussion. Only randomised controlled trials (RCTs) and full economic evaluations comparing topotecan to non-topotecan regimens were included. All stages of therapy and disease were considered, and the outcomes included were survival, response, symptom relief, quality of life, adverse effects and costs. METHODS: DATA EXTRACTION STRATEGY: Data were extracted into an Access database by one reviewer and checked by a second. Any disagreements were resolved through discussion. METHODS: QUALITY ASSESSMENT STRATEGY: Two reviewers, using specified criteria, independently assessed the quality of the clinical effectiveness studies and the economic evaluations. Any disagreements were resolved through discussion. METHODS: ANALYSIS STRATEGY: Due to the limited number of studies included in the review and the fact that they compared topotecan with different comparators, the out-come data could not be pooled statistically. Clinical effectiveness data are discussed separately under the different outcome subheadings. For time-to-event data, hazard ratios with 95% confidence intervals are presented where available, and for the remaining outcomes, relative risks are reported or calculated where sufficient data were available. Relative risk data are also presented in the form of Forest plots without pooled estimates. Economic data are presented in the form of a summary and critique of the evidence, and a grading (A-I) assigned to each study indicating the direction and magnitude of the cost-effectiveness data. RESULTS INCLUDED STUDIES: A total of 568 titles/abstracts were identified and screened for relevance. Full copies of 72 papers were assessed and seven published manuscripts reporting details of two studies of clinical effectiveness and one economic evaluation were included. Further details of the two clinical effectiveness studies and two new economic evaluations were identified from confidential company submissions. Overall, two international multicentre RCTs of effectiveness comparing topotecan with paclitaxel (trial 039) and topotecan with caelyx (trial 30-49) were included in the review. The three economic evaluations included in the review comprised one cost-minimisation analysis (CMA) comparing topotecan with caelyx, one cost-consequences analysis (CCA) comparing topotecan with paclitaxel, etoposide and altretamine and one cost-effectiveness analysis (CEA) comparing topotecan with paclitaxel. RESULTS: QUALITY OF CLINICAL EFFECTIVENESS DATA: Both clinical effectiveness studies (trial 30-49 and 039) were of reasonable quality, although it was unclear whether either performed valid intention-to-treat analyses. In addition, trial 30-49 failed to state whether the outcome assessors were blinded to treatment allocation. RESULTS --QUALITY OF ECONOMIC EVALUATIONS: The CCA (comparing topotecan with three comparators) was of poor quality and of little relevance to the UK NHS. The CMA and CEA were of reasonable quality overall and relevant to the UK NHS. However, both, in particular the CEA, suffered from methodological problems, and thus their findings should be interpreted with caution. RESULTS: ASSESSMENT OF CLINICAL EFFECTIVENESS: The assessment of clinical effectiveness was based on limited data. Only two trials with a total of 709 participants were identified. In general, with a few minor exceptions, there were no statistically significant differences between topotecan and paclitaxel, or topotecan and caelyx in survival, response rate, median time to response, median duration of response and quality of life. Significant differences that were reported were mainly identified in subgroup analyses (Pt-sensitive disease and disease without ascites) of questionable validity and their relevance to a general advanced ovarian cancer patient population undergoing second-line chemotherapy is unclear. However, statistically significant differences were observed in the incidence of adverse effects. Topotecan was associated with increased incidences of haematological toxicities (including neutropenia, leukopenia, anaemia and thrombocytopenia), alopecia, nausea and vomiting. Caelyx-treated patients suffered from significantly increased incidences of Palmar-Plantar erythrodysesthesia, stomatitis, mucous membrane disorders and skin rashes. Paclitaxel was associated with significant increases in alopecia, arthralgia, myalgia, neuropathy, paraesthesiae, skeletal pain and flushing. RESULTS: ASSESSMENT OF COST-EFFECTIVENESS: The assessment of cost-effectiveness was also based on limited data, with three evaluations identified, one of which was not relevant. The two remaining studies, comparing topotecan with paclitaxel (CEA) and topotecan with caelyx (CMA), both used effectiveness data from multicentre RCTs and based their costs on 1999/2000 UK sources. The evaluations were conducted from a UK NHS perspective and findings presented in GB pounds/Euros. Topotecan for the second-line treatment of advanced ovarian cancer was shown to be more cost-effective than paclitaxel (32,513 GB pounds versus 46,186 GB pounds per person in terms of any response (complete or partial), incremental cost-effectiveness = 3065 GB pounds) in all respects except cost per time without toxicity or symptoms, but less cost-effective than caelyx (14,023 GB pounds versus 9979 GB pounds per person regardless of whether the patient responded). However, direct comparisons of the cost findings between the two studies is difficult because they used different designs, different time horizons for the cost analyses and the findings were presented as costs per person for only patients who responded in one study (topotecan versus paclitaxel) and costs per person regardless of whether they responded in the other study (topotecan versus caelyx). CONCLUSIONS: This review indicates that there is little evidence in the form of RCTs on which to base an assessment of the effectiveness of topotecan as second-line therapy for advanced ovarian cancer. The evidence suggests there were no statistically significant differences overall between topotecan and paclitaxel, or topotecan and caelyx in clinical outcomes. However, statistically significant differences were observed in the incidence of adverse effects. The clinical significance of the findings is not discussed. Overall, the effects of topotecan could at best be described as modest, but the alternative agents offer no real advantages except fewer side-effects and possibly improved cost-effectiveness. Both of the clinical effectiveness studies on which this evidence is based had methodological flaws, the most serious being the lack of a blinded assessor in the topotecan versus caelyx trial, which is important for unbiased assessment of response outcomes. The economic evaluations also suffered from a number of potential problems. CONCLUSIONS: RECOMMENDATIONS FOR RESEARCH: Further good quality RCTs and CEAs are required comparing topotecan with other licensed and potentially useful (soon to be licensed) second-line treatments for ovarian cancer. At present, it is difficult to make any decisions about topotecan and other drugs for second-line therapy without good quality direct comparisons. In view of the ongoing studies identified, an update of the current review should be considered in approximately 18 months (Summer 2002) or possibly sooner if the recently commissioned National Institute for Clinical Excellence review of caelyx for ovarian cancer identifies additional data relevant to topotecan.

Antineoplastic Agents↗
PubMed2000

[Retrospective cohort study on the prognosis of chronic myeloid leukemia].

OBJECTIVE: To evaluate the prognostic factors of chronic myeloid leukemia (CML). METHODS: Survival curves were plotted according to the Kaplan-Meier method. Variables associated with prognosis were analyzed by Logrank test. A multivariate analysis of prognostic factors was performed using stepwise Cox model. RESULTS: Of the total 158 patients, the median survival time was 1,480 days. 5 years survival rate was 47.1% (95% CI, 36.7% - 56.9%). 10 years was 24.8% (95% CI, 15.0% - 35.8%). The predominant blastic crisis type is myeloblastic, myelomonocytic or monocytic(77.5%). The period from chronic phase to blastic phase was equal in myelosuppressive therapy group, non- myelosuppressive therapy group or altretamine (HMM) group. After evaluated by stepwise Cox's regression model, age>or=50 years, bone marrow blasts>or=0.05, bone marrow basophilic>or=0.05, Ph chromosome negative and HMM treatment were associated with poor prognosis. Hydroxyurea was always associated with longer survival. CONCLUSION: Age, Ph chromosome, bone marrow blasts and basophilic, and various treatment affected the survival of CML.

Adult↗
PubMed1992

Hypersensitivity reactions.

All cancer chemotherapeutic agents, except altretamine, the nitrosoureas, and dactinomycin, have produced at least an isolated instance of a HSR. Certain drugs, such as L-asparaginase and mitomycin (administered intravesically), cause HSRs of significant degree in approximately 10% of patients. All four types of HSRs are represented in the reactions produced by antitumor drugs, although Type I is the most common. Some of the Type I reactions are IgE-mediated, and others are probably mediated by nonspecific release of vasoactive substances from targets such as mast cells. It is possible to continue therapy with some drugs, despite a prior HSR, if the prophylactic measures outlined in Table 2 are taken. An example of this is provided by taxol in which the lengthening of the infusion time and the administration of preventive medication allowed some patients to continue taxol therapy. The mechanisms of the HSRs have been carefully assessed in only a minority of patients who sustained such toxicity. Such evaluation would increase our understanding of this form of drug toxicity and perhaps lead to means of effectively reducing the risk and severity.

Antibiotics, Antineoplastic↗
PubMed1993

Gynecologic malignancies.

No new publication appeared in the past year on early stage ovarian cancer. The current GOG study will help determine the relative benefits and toxicities of intraperitoneal P32 versus cyclophosphamide and cisplatin in this group of patients. Recent studies in advanced ovarian carcinoma suggest a modest additional benefit for multidrug regimens, but cisplatin and cyclophosphamide remains an acceptable first line treatment for stage III and IV disease. Additional information on the use of carboplatin in advanced disease has been published, and this agent is now accepted as part of standard first line treatment programs. Platinum-based chemotherapy continues to be the mainstay of treatment for recurrent disease. With the commercial availability of taxol, a new salvage treatment is now available. Taxol will be increasingly studied as a part of front-line therapy as well as its role in the salvage setting. Altretamine and ifosfamide appear to have activity even in some patients with platinum-resistant disease, but these drugs will not likely have a major impact on ovarian cancer treatment. The use of high-dose chemotherapy with autologous bone marrow or peripheral stem cell support offers an exciting and potentially beneficial approach for patients with poor prognosis disease. The use of intraperitoneal chemotherapy and biologic agents continues to be problematic, and additional improvements are needed before they are considered useful outside of a research setting. With the exception of P32 for early stage disease, radiation therapy is likely to continue to play a minor role in the treatment of ovarian cancer. Few studies involving non-epithelial ovarian carcinomas were published during the past year. A definitive report was published demonstrating the activity of cisplatin-based chemotherapy (BEP) in patients with advanced dysgerminoma. Chemotherapy which preserves fertility provides an effective alternative to irradiation. Cisplatin-based chemotherapy was active in mixed mullerian tumors of the ovary although the prognosis of these patients was worse than patients with epithelial ovarian cancer. Concurrent chemotherapy added to irradiation has not improved survival over radiotherapy alone in patients with cancer of the uterine cervix. Patients still failed locally and distantly. Extended field irradiation to involved paraaortic lymph nodes with weekly cisplatin generated promising pilot data. Randomized trials evaluating the use of neoadjuvant chemotherapy prior to pelvic radiotherapy showed no benefit and increased toxicity. Ifosfamide alone or in combination regimens is an active drug but with serious side effects which require careful monitoring.(ABSTRACT TRUNCATED AT 400 WORDS)

Combined Modality Therapy↗
PubMed1979

Ovarian cancer. Effective treatment after alkylating-agent failure.

Combination chemotherapy consisting of hexamethylmelamine and cisplatin, alone or with doxorubicin hydrochloride, was given to 27 patients with advanced ovarian cancer who had disease progression with therapy including alkylating agents. Eighteen (67%) had greater than 50% regression of measurable disease or disease that could be evaluated but not measured, for a projected median duration of seven months. The projected median survival for all patients is nine months from the time of entry into the study and 33 months from the time of diagnosis of ovarian cancer. The treatment could be readily administered on an outpatient basis with a regimen of hydration and diuresis that nearly completely prevented platinum-induced renal tubular damage. Myelosuppression was severe in 11 patients (40%), but there was no treatment-related deaths. Agents of such high activity should be considered as components of initial therapy for stage III and IV cancers.

Adenocarcinoma↗
PubMedDate not supplied

Evaluation of the porphyrinogenic risk of antineoplastics.

The use of antineoplastics is common in cancer therapy, and some of them have been associated with the development of porphyria in patients with cancer. However, knowledge of their effects on the haeme metabolic pathway is at present scarce and unclear. So, the present study evaluates the porphyrinogenic ability of nine antineoplastics (both alkylating and non-alkylating). These were tested either alone or in conjunction with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (latent porphyria model) in chick embryos and in mice. The results obtained suggest that the use of cyclophosphamide, azathioprine, 5-fluorouracil, busulphan, procarbazine and hexamethylmelamine be avoided in the treatment of porphyric patients. On the other hand, dacarbazine, chlorambucil and melphalan are non-porphyrinogenic. We also provide evidence showing that neither the presence of the mustard group in the structure of the antineoplastic nor alterations in ferrochelatase or protoporphyrinogen oxidase activities are responsible for the porphyrinogenic ability of cyclophosphamide.

Alkylating Agents↗
PubMed1976

Hexamethylmelamine. An evaluation of its role in the therapy of cancer.

Hexamethylmelamine (HMM) has been undergoing clinical trials for about a decade under the sponsorship of the National Cancer Institute. It has been tested in Phase II and III cooperative group studies and has a wide spectrum of activity in solid tumors. Its activity is most marked in ovarian cancer, lymphomas, and carcinoma of the cervix; the drug is also active in bronchogenic carcinoma and carcinoma of the breast. Considerable clinical evidence suggests a lack of cross-resistance between HMM and alkylating agents. the currently popular dose is 300 mg/m2/day p.o. for indefinite periods if tolerated. The dose-limiting toxicity is neurologic, but gastrointestinal side effects and a moderate degree of myelosuppression are also observed. Combination chemotherapy using HMM is underway in ovarian and lung cancer. Futher exploration of its activity as a single agent in tumors such as those of the bladder, prostate, and uterus, and in combination chemotherapy in lymphomas, and mammary, cervical, and pulmonary tumors is warranted.

Altretamine↗
PubMed1977

Advances in the staging and treatment of ovarian cancer.

The age adjusted death rate for ovarian cancer has remained unchanged for the past 20 years. Recent data obtained by staging ovarian cancer patients with lymphangiography and peritoneoscopy demonstrated that many patients with apparently localized disease actually have occult dissemination within the abdomen. These new staging techniques plus the determination of the histologic grade of anaplasia may permit a more precise determination of a patient's prognosis and therefore better design of therapeutic stategy. Radiotherapeutic techniques are being adapted to attempt to treat some areas of occult disease. Numerous single chemotherapeutic agents are capable of producing objective tumor responses. Preliminary data suggest that combination chemotherapy can increase the objective response rate above that seen with single agents. Longer follow-up is necessary to determine whether combination chemotherapy can prolong survival.

Alkylating Agents↗
PubMed1977

Ovarian cancer: use of multiple modality programs involving surgery, radiation therapy and chemotherapy.

Appreciating the past reports of effectiveness for various therapeutic modalities in ovarian cancer, the Gynecologic Oncology Group activated eight protocols. Three involved epithelial lesions with randomized multimodality trials alone or in combination. The other protocols were devoted to registration of rare tumor case reports. Conclusions are still difficult to reach due to inconsistencies in pathologic diagnoses and deficiencies in radiation therapy, chemotherapy and surgery inherent in the initial phases of group development by diverse specialist in oncology. Adjuvant therapy for early cancer seems to have no advantage. Single drug, melphalan therapy may be as effective as multi-drug, irradiation or combined drug-irradiation therapy and less toxic. For the rare tumors, preliminary results suggest therapeutic advantage for at least one triple drug program in malignant teratoma. With the lessons of the past, it is anticipated that new studies briefly described herewith may be more effectively applied.

Altretamine↗
PubMed1978

Hexamethylmelamine in alkylating agent-resistant ovarian carcinoma.

Twenty-one patients with advanced ovarian cancer proven resistant to standard alkylating chemotherapy were evaluated in a prospective study of Hexamethylmelamine. All but three patients received 8 mg/kg daily with dose modifications appropriate to the degree of toxicity; the latter three patients were treated on an intermittent 14 day course of 8 mg/kg daily. Six patients (28%) experienced an objective response with a median duration of 2.5 months (range 1--5 months). The toxic effects requiring dose modification were gastrointestinal in 57%, hematologic in 62%, and neurologic in 28.5%. An average of 60.5% of the total projected dose was tolerated for a median of 44 days (range 7--113). Twelve patients (57%) experienced severe toxicity requiring discontinuation of therapy. It is apparent from this study that Hexamethylmelamine is an active agent in ovarian cancer and is not invariably cross-resistant to conventional alkylating agent therapy. These two characteristics make it an attractive agent for use in combination. Its toxicity in previously treated patients in the schedules used here, however, is substantial.

Adenocarcinoma↗
PubMed1981

Doxorubicin-hexamethylmelamine therapy of small cell carcinoma of the lung.

Eighteen patients with small cell carcinoma of the lung treated with doxorubicin hydrochloride and hexamethylmelamine are presented. Fifteen of these patients had extensive disease at presentation. Four patients in this group died after one or fewer courses of chemotherapy. The median duration of survival for the entire group of patients is 15 months. Six patients are alive from 18 to 56 months without evidence of disease. Drug toxicity was minimal and well tolerated, which permitted this regimen to be given in an outpatient setting.

Adult↗
PubMed1981

Advanced ovarian carcinoma: a prospective and randomized clinical trial of cyclophosphamide versus combination cytotoxic chemotherapy (Hexa-CAF).

Fifty-seven evaluable patients with advanced ovarian carcinoma were randomized to receive either a combination of hexamethylmelamine, cyclophosphamide, methotrexate and 5-fluorouracil (Hexa-CAF) or high-dose cyclophosphamide alone given intravenously intermittently. Objective responses were seen in 62% of patients receiving cyclophosphamide alone, and 36% of patients in the Hexa-CAF regimen, this difference being statistically significant (P less than 0.05). The median duration of objective response (10 months vs. 9 months) and the median survival (11 months vs. 10 months) were greater in the cyclophosphamide group, but these differences were not statistically significant. It is concluded that there is no therapeutic advantage for the Hexa-CAF protocol over the alkylating agent used alone.

Adenocarcinoma, Mucinous↗