1. CISPLATIN AND CARBOPLATIN. These agents are from the same class of drugs but with different toxicity. A phase III trial conducted by the Gynecologic Oncology Group (GOG-158), showed that carboplatin/paclitaxel treatment offered efficacy comparable with that of cisplatin/paclitaxel, but did not exhibit the cumulative nephrotoxicity associated with cisplatin therapy. Vigorous hydration or diuresis is necessary during cisplatin administration to minimize the risk and severity of acute nephrotoxicity. Neurotoxicity, including paresthesias and permanent high-tone hearing loss, also occurs in up to 23% and 45% of the patients receiving cisplatin therapy, respectively. In addition, the risk of an allergic hypersensitivity response increases with continued use. Prophylactic treatment with steroids and antihistamines and a slow infusion rate may minimize this risk, although fatal anaphylaxis has still been reported despite these precautions. Gastrointestinal adverse events are also common with cisplatin therapy and may be acute or delayed in onset. The resulting nausea and vomiting are the major complaints among cisplatin-treated patients. Use of 5-hydroxytryptamine 3 inhibitors (e.g., granisetron, ondansetron, and tropisetron) can reduce the incidence and severity of these effects(1).

2. PACLITAXEL. Is a drug that promotes early microtubule assembly and prevents depolimerization necessary for normal mitosis. The result is a blockade of cell division and finally cell death. The side effects of paclitaxel are: potential reaction caused by hypersensitivity reactions, bone marrow depression(9) with infection and bleeding, sensory neuropathy, alteration of skin integrity (alopecia, onycholysis), alteration in nutrition (by nausea and vomiting, diarrhea, stomatitis, hepatotoxicity), alteration of circulation related to hypotension, arrhythmia, fatigue, arthralgias, myalgias. FDA: minor symptoms such as flushing, skin reactions, dyspnea, hypotension, or tachycardia do not require interruption of therapy. However, severe reactions, such as hypotension requiring treatment, dyspnea requiring bronchodilators, angioedema, or generalized urticaria require immediate discontinuation of Paclitaxel and aggressive symptomatic therapy. Patients who have developed severe hypersensitivity reactions should not be rechallenged with Paclitaxel. Cardiovascular toxicity, hypotension, bradycardia, and hypertension have been observed during administration of Paclitaxel, but generally do not require treatment. There is limited hepatic toxicity of Paclitaxel, serum total bilirubin >2 times ULN. Extreme caution should be exercised when administering Paclitaxel to such patients, with dose reduction as recommended. Paclitaxel was not mutagenic in the Ames test or the CHO/HGPRT gene mutation assay. Paclitaxel seems to have in impact in fertility(2,3,4).

3. GEMCITABINE. The main side effects are: hematologic (very common - 10% or more): anemia (68%), neutropenia (63%), leucopenia (62%), thrombocytopenia (24%). Gastrointestinal (very common - 10% or more): nausea/vomiting (69%), diarrhea (19%), stomatitis (11%), stomatitis and ulceration of the mouth (11%), hepatic - increased ALT (68%), increased AST (67%), increased alkaline phosphatase (55%), hyperbilirubinemia (13%). Renal failure may not be reversible, even upon discontinuation of therapy. Very common (10% or more): proteinuria (45%), hematuria (35%), increased BUN (16%), common (1% to 10%): increased creatinine (8%), uncommon (0.1% to 1%): renal failure, hemolytic-uremic syndrome. Other toxicity: the flu-like symptoms usually take place a few hours after drug administration. The symptoms are usually self-limiting and recovery is generally within 24 to 48 hours. Dermatologic: rash was generally a macular or finely granular maculopapular pruritic eruption, mild to moderate in severity, involving the trunk and extremities. Alopecia is usually minimal. Respiratory toxicity is very common (10% or more): dyspnea (23%), common (1% to 10%): cough, rhinitis. Uncommon (0.1% to 1%): interstitial pneumonitis, bronchospasm. Rare (0.01% to 0.1%): pulmonary edema, adult respiratory distress syndrome (ARDS). Very rare (less than 0.01%): respiratory failure/ death. A rapid response following the administration of corticosteroids would mean the respiratory problem was probably due to a hypersensitivity reaction. Other toxicity: headache, insomnia, somnolence, paraesthesia (1% to 10%)(5,6,7).

4. DOXORUBICINE. Cardiovascular side effects. The risk of heart failure is significantly increased after total doses of 550 mg/m2 (350 to 400 mg/m2 if there is history of prior radiation therapy which included the heart or the area around it or use of other potentially cardiotoxic agents, such as cyclophosphamide). Hematologic. The leukocyte count usually reaches a nadir at 10 to 14 days after treatment. Dermatologic: side effects have included reversible alopecia (scalp, pubis and/or axilla). Less commonly, hyperpigmentation of nailbeds and dermal creases and oncholysis (nail loss) have been reported. Local side effects have included i.v. site problems such as phlebosclerosis (especially when a single vein and/or a small vein are used) and extravasation tissue necrosis. Extravasation may occur and the standard of care is ice packs for 24 hours for acute extravasation injury; some advocate topical application of 10% to 99% dimethyl sulfoxide (DMSO) with ice packs. However, because of the inconsistent results associated with some of these therapies and the progressive nature of extravasation reactions, plastic surgery consultation is generally recommended. Hypersensitivity reactions have occasionally been reported, and may include fever, chills, urticaria, angioneurotic edema or anaphylaxis. Renal side effects have included rare cases(8).

5. LIPOSOMAL DOXORUBICIN (CAELYX) toxicity: caused by free radical damage to the myocytes. Acute cardio­myopathy - during/immediately after a single dose of doxorubicin. Chronic cardiomyopathy - result of cumulative build up of doxorubicin. Late-onset cardiomyopathy may occur up to 15 years after treatment. Protection by reducing the dose of doxorubicin. Redness, tenderness, and pealing skin can be managed with pyridoxine and corticosteroids. Other side effects are similar with doxorubicin by i.v. administratin(9).

6. EPIRUBICIN has aproximatly the same side effects like doxorubicine but the cumulative dose greater comparable to doxorubicin and can reach 900 mg(10).

7. TOPOTECAN. In the event of severe febrile neutropenia (defined as <1,000 cells/mm3 with temperature of 38°C or 100.4°F), reduce the dose of Topotecan hydrochloride for injection to 0.6 mg/m2 for subsequent courses. In severe febrile neutropenia, administer G-CSF following the subsequent course (before resorting to dose reduction) starting from day 4 of the course (24 hours after completion of administration of Topotecan hydrochloride for injection). If febrile neutropenia occurs despite the use of G-CSF, reduce the dose of Topotecan to 0.45 mg/m2 for subsequent courses. No dosage adjustment of Topotecan hydrochloride for injection appears to be required for patients with mild renal impairment (Clcr 40 to 60 mL/min). Dosage adjustment of Topotecan hydrochloride for injection to 0.75 mg/m2 is recommended for patients with moderate renal impairment (20 to 39 mL/min)(11). Other common neurological, dermatological, and gastrointestinal toxicity are similar to other cytostatics. Some particularities of side effects are pain, including abdominal pain or cramping, arthralgia, bone pain, chest pain (non-cardiac and non-pleuritic), dyspareunia, earache, headache, hepatic pain, myalgia, neuropathic pain, pelvic pain, rectal or perirectal pain, tumor pain(12,13,14).

8. DOCETAXEL has a similar toxicity as Paclitaxel. The most common adverse reactions across all indications include infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions, and myalgia(15).

9. TRABECTEDIN. The most common grade 3/4 drug related side effects were fatigue, nausea and vomiting. Neu­tropenia and thrombocytopenia were the most common grade 3/4 hematologic side effects, but they were transient with rapid recovery. Liver related grade 3/4 toxicities were mostly limited to transient elevation of AST and ALT with bilirubin being affected uncommonly(16,17).

10. BEVACIZUMAB. Hypertension is the most common toxicity associated with bevacizumab treatment. Standard antihypertensive therapy, typically angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, calcium channel blockers, or diuretics, can be used to control grade-3 hypertension, and bevacizumab can be continued without dose modification. A specific side effect is wound healing complications which have been described in patients who underwent primary cancer surgery within 28-60 days before starting bevacizumab treatment. Other event described after surgery (sixty-day postoperative) included abnormal healing, wound dehiscence, delayed wound healing, bowel perforation, fistula, abscess, and hemorrhage. In the preliminary BRITE analysis, 1% of the patients had postoperative complications. Venous and arterial thrombotic events ATE (any grade) during bevacizumab treatment should discontinue treatment permanently. Epistaxis was the most common bleeding event encountered, and if repeated grade 3 or a new grade 4 hemorrhagic event, bevacizumab should be permanently discontinued. Other side effects are very rare(18,19).

11. OLAPARIB. The following side effects are common (occurring in more than 30%) for patients taking olaparib: anemia, nausea, fatigue, neutropenia, thrombocytopenia, abdominal pain, upper respiratory tract infection, musculoskeletal pain, diarrhea, constipation, urinary tract infection. Some studies described acute leukemia, which was attributed to COPD, cerebrovascular accident, intestinal perforation, pulmonary embolism, sepsis, and suture rupture(20,21,22,23).